Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2007 |
| Tipo de documento: | Dissertação |
| Idioma: | por |
| Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFC |
| Texto Completo: | http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1114 |
Resumo: | The monoterpenes α- and β-pinene are constituents commonly found in several essential oils obtained from plants in Brazilian northeast such as âmalva-santaâ and âeucaliptoâ, which are used in folk medicine to treat respiratory and gastrointestinal dysfunctions. Myorelaxant actions are due to the presence of these constituents in their essential oils. The present work aimed to further study the pharmacological effects of these compounds on smooth muscle gastrointestinal contractility as well as on liquid gastric emptying in rats. Wistar rats (200-250 g) were used, sacrificed by cervical dislocation. Strips were carefully obtained from gastric fundus, duodenum and ileum, and were maintained in Tyrodeâs solution. Isometric contractions were recorded through force transducers coupled to a computerized data acquisition system. Solutions containing α- or β-pinene were prepared with Tween 80 (final concentration ≤ 0,2% v/v). Solely used, α- or β-pinene decreased duodenal basal tonus with IC50 value corresponding to 655.1 ÂM and 810.2 ÂM, respectively. Submaximal contractions induced by K+ (60 mM, K60) or acetylcholine (ACh, 3 ÂM) were inhibited, in a concentration-dependent manner (p < 0.001, ANOVA), with IC50 values of 790.0 [580.2-1007.4] e 760.0 [650.6-870.8] ÂM, respectively to α-pinene and 770.1 [500.3-1180.5] e 620.7 [520.9-750.2] ÂM, respectively to β-pinene. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM) in medium without Ca2+ with EGTA (0.2 mM), ACh (3 ÂM)-induced phasic contractions were inhibited from 18.4 Â 3.3% to 7.7 Â 1.5% and 5.0 Â 1.2% of K60, respectively. In tissues maintained under Ca2+-free conditions (in medium containing EGTA 0.2 mM) and in presence of K+ (60 mM) or ACh (3 ÂM), tonic contractions induced by Ca2+ addition were reduced from 50.2 Â 3.3% and 53.9 Â 5.2%, respectively to values corresponding to 10.6 Â 2.6 % and 24.4 Â 4.1 % to experiments with α-pinene and 6.6 Â 1.1 % and 10.9 Â 3.5 % to experiments with β-pinene, respectively. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM), ACh (60 ÂM)-induced tonic contractions, in verapamil (3 ÂM)-containing medium, were inhibited from 29.0 Â 4.1 % to 10.6 Â 2.7 % and 12.5 Â 2.2 % of the K60, respectively. The caffeine (20 mM)-induced contractile response in normal Tyrodeâs solution was potentiated from 47.8 Â 3.2 % to 72.1 Â 9.0 and 88.8 Â 10.6 % of the control response in virtue of α- (1 mM) or β-pinene (1 mM) presence, respectively. In EGTA-containing Ca2+-free medium, the contractile response to caffeine was reduced to 9.5 Â 3.5%. Under these conditions, and in presence of α- (1 mM) or β-pinene (1 mM), this response was not significantly altered, with values corresponding to 7.2 Â 2.2 e 4.7 Â 1.3 %, respectively. In verapamil- and EGTA-containing Ca2+-free medium, after depletion of the intracellular Ca2+ stores by CCh (100 ÂM), the contractions induced by Ca2+ addition were potentiated by the presence of α- (1 mM) or β-pinene (1 mM) from 30.7 Â 2.1 % to 80.6 Â 4.7 and 51.3 Â 7.6 %, respectively (p < 0.05, Bonferroniâs test). In gastrointestinal dye fractional retention studies, α- or β-pinene increased the rat liquid gastric emptying. On the other hand, they did not alter the ACh-induced contractions on gastric fundus strips. Our study firstly shows that, both α- and β-pinene have prokinetic properties in rats. In isolated tissues, they did not affect cholinergic contractions on gastric fundus strips, but are myorelaxant compounds on rat duodenal preparations, probably by an interference with cellular mechanisms mediated by IP3 release. Moreover, α- and β-pinene activate capacitative Ca2+ entry to intracellular milieu after Ca2+ stores depletion |
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info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPropriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃticoPharmacological properties of the monoterpenes α- and β-pinene on rat gastrointestinal smooth muscle: myorelaxant and prokinetic effects2007-07-20Pedro Jorge Caldas MagalhÃes38546620334http://lattes.cnpq.br/0057645238802910ArmÃnio Aguiar dos Santos21268789372http://lattes.cnpq.br/6367176618425888 Ricardo Brandt de Oliveira23267488834http://lattes.cnpq.br/052005332707497089087690304http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4716074E7Davi Matthews JucÃUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em FarmacologiaUFCBRAlfa-pinenoBeta-pineno Terpenos MÃsculo liso Contratilidade Intestino Esvaziamento GÃstricoAlpha-pineneBeta-pinene Terpenes Smooth Muscle Contratility Intestine Gastric EmptyingFARMACOLOGIAThe monoterpenes α- and β-pinene are constituents commonly found in several essential oils obtained from plants in Brazilian northeast such as âmalva-santaâ and âeucaliptoâ, which are used in folk medicine to treat respiratory and gastrointestinal dysfunctions. Myorelaxant actions are due to the presence of these constituents in their essential oils. The present work aimed to further study the pharmacological effects of these compounds on smooth muscle gastrointestinal contractility as well as on liquid gastric emptying in rats. Wistar rats (200-250 g) were used, sacrificed by cervical dislocation. Strips were carefully obtained from gastric fundus, duodenum and ileum, and were maintained in Tyrodeâs solution. Isometric contractions were recorded through force transducers coupled to a computerized data acquisition system. Solutions containing α- or β-pinene were prepared with Tween 80 (final concentration ≤ 0,2% v/v). Solely used, α- or β-pinene decreased duodenal basal tonus with IC50 value corresponding to 655.1 ÂM and 810.2 ÂM, respectively. Submaximal contractions induced by K+ (60 mM, K60) or acetylcholine (ACh, 3 ÂM) were inhibited, in a concentration-dependent manner (p < 0.001, ANOVA), with IC50 values of 790.0 [580.2-1007.4] e 760.0 [650.6-870.8] ÂM, respectively to α-pinene and 770.1 [500.3-1180.5] e 620.7 [520.9-750.2] ÂM, respectively to β-pinene. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM) in medium without Ca2+ with EGTA (0.2 mM), ACh (3 ÂM)-induced phasic contractions were inhibited from 18.4  3.3% to 7.7  1.5% and 5.0  1.2% of K60, respectively. In tissues maintained under Ca2+-free conditions (in medium containing EGTA 0.2 mM) and in presence of K+ (60 mM) or ACh (3 ÂM), tonic contractions induced by Ca2+ addition were reduced from 50.2  3.3% and 53.9  5.2%, respectively to values corresponding to 10.6  2.6 % and 24.4  4.1 % to experiments with α-pinene and 6.6  1.1 % and 10.9  3.5 % to experiments with β-pinene, respectively. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM), ACh (60 ÂM)-induced tonic contractions, in verapamil (3 ÂM)-containing medium, were inhibited from 29.0  4.1 % to 10.6  2.7 % and 12.5  2.2 % of the K60, respectively. The caffeine (20 mM)-induced contractile response in normal Tyrodeâs solution was potentiated from 47.8  3.2 % to 72.1  9.0 and 88.8  10.6 % of the control response in virtue of α- (1 mM) or β-pinene (1 mM) presence, respectively. In EGTA-containing Ca2+-free medium, the contractile response to caffeine was reduced to 9.5  3.5%. Under these conditions, and in presence of α- (1 mM) or β-pinene (1 mM), this response was not significantly altered, with values corresponding to 7.2  2.2 e 4.7  1.3 %, respectively. In verapamil- and EGTA-containing Ca2+-free medium, after depletion of the intracellular Ca2+ stores by CCh (100 ÂM), the contractions induced by Ca2+ addition were potentiated by the presence of α- (1 mM) or β-pinene (1 mM) from 30.7  2.1 % to 80.6  4.7 and 51.3  7.6 %, respectively (p < 0.05, Bonferroniâs test). In gastrointestinal dye fractional retention studies, α- or β-pinene increased the rat liquid gastric emptying. On the other hand, they did not alter the ACh-induced contractions on gastric fundus strips. Our study firstly shows that, both α- and β-pinene have prokinetic properties in rats. In isolated tissues, they did not affect cholinergic contractions on gastric fundus strips, but are myorelaxant compounds on rat duodenal preparations, probably by an interference with cellular mechanisms mediated by IP3 release. Moreover, α- and β-pinene activate capacitative Ca2+ entry to intracellular milieu after Ca2+ stores depletionα- e β-pineno sÃo monoterpenos constituintes do Ãleo essencial de plantas encontradas no Nordeste do Brasil como a malva-santa e o eucalipto que, na medicina popular, sÃo usadas no tratamento de distÃrbios intestinais e respiratÃrios. As aÃÃes miorrelaxantes desses Ãleos essenciais sÃo atribuÃdas à presenÃa de α- e de β-pineno. Nosso objetivo foi estudar mais detalhadamente os efeitos desses constituintes sobre a contratilidade do mÃsculo liso gastrintestinal e sobre o esvaziamento gÃstrico de lÃquido em ratos. No presente estudo, foram usados ratos Wistar machos (200-250g) sacrificados por deslocamento cervical. Tiras de duodeno, Ãleo e fundo de estÃmago foram cortados e mantidos em Tyrode. As contraÃÃes isomÃtricas foram registradas atravÃs de transdutores de forÃa conectados a sistema computadorizado. SoluÃÃes contendo α- ou β-pineno foram preparadas em Tween 80 (concentraÃÃo final ≤ 0,2% v/v). Usados isoladamente, α- e β-pineno diminuÃram o tÃnus basal em duodeno com CI50 de 655,1 e 810,2 ÂM, respectivamente. ContraÃÃes submaximais induzidas por K+ (60 mM, K60) ou acetilcolina (ACh, 3 ÂM) foram inibidas, de maneira concentraÃÃo-dependente (p < 0,001, ANOVA), com valores de CI50 correspondentes a 790,0 [580,2-1007,4] e 760,0 [650,6-870,8] ÂM, respectivamente, para o α-pineno e 770,1 [500,3-1180,5] e 620,7 [520,9-750,2] ÂM para o β-pineno, respectivamente. Em preparaÃÃes prÃ-tratadas com 1 mM de α- ou β-pineno, a contraÃÃo fÃsica induzida por ACh (3 ÂM) em meio sem Ca2+ contendo EGTA (0,2 mM) foi reduzida de 18,4  3,3 % para 7,7  1,5 % e 5,0  1,2 % da contraÃÃo K60, respectivamente. A contraÃÃo tÃnica induzida por adiÃÃo de Ca2+ (2 mM) em preparaÃÃes mantidas na presenÃa de K+ (60 mM) ou ACh (3 ÂM), em meio sem Ca2+ contendo EGTA (0,2 mM), foi reduzida de 50,2  3,3 % e de 53,9  5,2 % para 10,6  2,6 % e 24,4  4,1 % pelo α-pineno e 6,6  1,1 % e 10,9  3,5 % pelo β-pineno, respectivamente. Em preparaÃÃes prÃ-tratadas com 1 mM de α- ou β-pineno, a contraÃÃo tÃnica induzida por ACh (60 ÂM) em Tyrode normal contendo verapamil (3 ÂM) foi reduzida de 29,0  4,1 % para 10,6  2,7 % e 12,5  2,2 % da K60, respectivamente. A resposta contrÃtil induzida pela cafeÃna (20 mM) em Tyrode normal foi potencializada de 47,8  3,2 % para 72,1  9,0 e 88,8  10,6 % da resposta controle pelo prÃ-tratamento da preparaÃÃo com α- ou β-pineno, respectivamente. Em meio sem Ca2+ com EGTA, a resposta contrÃtil da cafeÃna (20 mM) foi reduzida para 9,5  3,5 %. Sob essa condiÃÃo e, na presenÃa de α- ou β-pineno, a resposta nÃo foi alterada significativamente, correspondendo a 7,2  2,2 e 4,7  1,3 %, respectivamente. ApÃs esgotamento dos estoques intracelulares com CCh (100 mM), a contraÃÃo induzida por adiÃÃo de Ca2+ (2 mM), em meio sem Ca2+ com EGTA (0,2 mM) e verapamil (3 ÂM), foi potencializada pela adiÃÃo prÃvia de α- ou β-pineno de 30,7  2,1 % para 80,6  4,7 e 51,3  7,6 %, respectivamente (p < 0,05, teste de Bonferroni). Em estudos de retenÃÃo fracional de corante no trato gastrintestinal, o α- e o β-pineno aumentaram o esvaziamento gÃstrico, porÃm, a contratilidade induzida por ACh (3 ÂM) em tiras de fundo de estÃmago in vitro nÃo foi alterada pela presenÃa prÃvia de α- e β-pineno. O presente trabalho demonstra, pela primeira vez, que os monoterpenos α- e β-pineno apresentam efeito procinÃtico em ratos. Em tecidos isolados, nÃo afetam a contraÃÃo colinÃrgica em tiras de estÃmago, mas apresentam atividade miorrelaxante em tecido duodenal, por provÃvel interferÃncia com os mecanismos celulares mediados pela formaÃÃo de IP3. AlÃm disso, como demonstrado em Ãleo de rato, esses monoterpenos provavelmente ativam as vias de entrada de Ca2+ para a cÃlula em situaÃÃes de depleÃÃo dos estoques intracelularesConselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicohttp://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1114application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:14:00Zmail@mail.com - |
| dc.title.pt.fl_str_mv |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico |
| dc.title.alternative..fl_str_mv |
Pharmacological properties of the monoterpenes α- and β-pinene on rat gastrointestinal smooth muscle: myorelaxant and prokinetic effects |
| title |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico |
| spellingShingle |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico Davi Matthews Jucà Alfa-pineno Beta-pineno Terpenos MÃsculo liso Contratilidade Intestino Esvaziamento GÃstrico Alpha-pinene Beta-pinene Terpenes Smooth Muscle Contratility Intestine Gastric Emptying FARMACOLOGIA |
| title_short |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico |
| title_full |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico |
| title_fullStr |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico |
| title_full_unstemmed |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico |
| title_sort |
Propriedades farmacolÃgicas dos monoterpenos α- e β-pineno no mÃsculo liso gastrintestinal de ratos: efeito miorrelaxante e prÃ-cinÃtico |
| author |
Davi Matthews Jucà |
| author_facet |
Davi Matthews Jucà |
| author_role |
author |
| dc.contributor.advisor1.fl_str_mv |
Pedro Jorge Caldas MagalhÃes |
| dc.contributor.advisor1ID.fl_str_mv |
38546620334 |
| dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/0057645238802910 |
| dc.contributor.referee1.fl_str_mv |
ArmÃnio Aguiar dos Santos |
| dc.contributor.referee1ID.fl_str_mv |
21268789372 |
| dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/6367176618425888 |
| dc.contributor.referee2.fl_str_mv |
Ricardo Brandt de Oliveira |
| dc.contributor.referee2ID.fl_str_mv |
23267488834 |
| dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/0520053327074970 |
| dc.contributor.authorID.fl_str_mv |
89087690304 |
| dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4716074E7 |
| dc.contributor.author.fl_str_mv |
Davi Matthews Jucà |
| contributor_str_mv |
Pedro Jorge Caldas MagalhÃes ArmÃnio Aguiar dos Santos Ricardo Brandt de Oliveira |
| dc.subject.por.fl_str_mv |
Alfa-pineno Beta-pineno Terpenos MÃsculo liso Contratilidade Intestino Esvaziamento GÃstrico |
| topic |
Alfa-pineno Beta-pineno Terpenos MÃsculo liso Contratilidade Intestino Esvaziamento GÃstrico Alpha-pinene Beta-pinene Terpenes Smooth Muscle Contratility Intestine Gastric Emptying FARMACOLOGIA |
| dc.subject.eng.fl_str_mv |
Alpha-pinene Beta-pinene Terpenes Smooth Muscle Contratility Intestine Gastric Emptying |
| dc.subject.cnpq.fl_str_mv |
FARMACOLOGIA |
| dc.description.sponsorship.fl_txt_mv |
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico |
| dc.description.abstract..fl_txt_mv |
The monoterpenes α- and β-pinene are constituents commonly found in several essential oils obtained from plants in Brazilian northeast such as âmalva-santaâ and âeucaliptoâ, which are used in folk medicine to treat respiratory and gastrointestinal dysfunctions. Myorelaxant actions are due to the presence of these constituents in their essential oils. The present work aimed to further study the pharmacological effects of these compounds on smooth muscle gastrointestinal contractility as well as on liquid gastric emptying in rats. Wistar rats (200-250 g) were used, sacrificed by cervical dislocation. Strips were carefully obtained from gastric fundus, duodenum and ileum, and were maintained in Tyrodeâs solution. Isometric contractions were recorded through force transducers coupled to a computerized data acquisition system. Solutions containing α- or β-pinene were prepared with Tween 80 (final concentration ≤ 0,2% v/v). Solely used, α- or β-pinene decreased duodenal basal tonus with IC50 value corresponding to 655.1 ÂM and 810.2 ÂM, respectively. Submaximal contractions induced by K+ (60 mM, K60) or acetylcholine (ACh, 3 ÂM) were inhibited, in a concentration-dependent manner (p < 0.001, ANOVA), with IC50 values of 790.0 [580.2-1007.4] e 760.0 [650.6-870.8] ÂM, respectively to α-pinene and 770.1 [500.3-1180.5] e 620.7 [520.9-750.2] ÂM, respectively to β-pinene. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM) in medium without Ca2+ with EGTA (0.2 mM), ACh (3 ÂM)-induced phasic contractions were inhibited from 18.4 Â 3.3% to 7.7 Â 1.5% and 5.0 Â 1.2% of K60, respectively. In tissues maintained under Ca2+-free conditions (in medium containing EGTA 0.2 mM) and in presence of K+ (60 mM) or ACh (3 ÂM), tonic contractions induced by Ca2+ addition were reduced from 50.2 Â 3.3% and 53.9 Â 5.2%, respectively to values corresponding to 10.6 Â 2.6 % and 24.4 Â 4.1 % to experiments with α-pinene and 6.6 Â 1.1 % and 10.9 Â 3.5 % to experiments with β-pinene, respectively. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM), ACh (60 ÂM)-induced tonic contractions, in verapamil (3 ÂM)-containing medium, were inhibited from 29.0 Â 4.1 % to 10.6 Â 2.7 % and 12.5 Â 2.2 % of the K60, respectively. The caffeine (20 mM)-induced contractile response in normal Tyrodeâs solution was potentiated from 47.8 Â 3.2 % to 72.1 Â 9.0 and 88.8 Â 10.6 % of the control response in virtue of α- (1 mM) or β-pinene (1 mM) presence, respectively. In EGTA-containing Ca2+-free medium, the contractile response to caffeine was reduced to 9.5 Â 3.5%. Under these conditions, and in presence of α- (1 mM) or β-pinene (1 mM), this response was not significantly altered, with values corresponding to 7.2 Â 2.2 e 4.7 Â 1.3 %, respectively. In verapamil- and EGTA-containing Ca2+-free medium, after depletion of the intracellular Ca2+ stores by CCh (100 ÂM), the contractions induced by Ca2+ addition were potentiated by the presence of α- (1 mM) or β-pinene (1 mM) from 30.7 Â 2.1 % to 80.6 Â 4.7 and 51.3 Â 7.6 %, respectively (p < 0.05, Bonferroniâs test). In gastrointestinal dye fractional retention studies, α- or β-pinene increased the rat liquid gastric emptying. On the other hand, they did not alter the ACh-induced contractions on gastric fundus strips. Our study firstly shows that, both α- and β-pinene have prokinetic properties in rats. In isolated tissues, they did not affect cholinergic contractions on gastric fundus strips, but are myorelaxant compounds on rat duodenal preparations, probably by an interference with cellular mechanisms mediated by IP3 release. Moreover, α- and β-pinene activate capacitative Ca2+ entry to intracellular milieu after Ca2+ stores depletion |
| dc.description.abstract.por.fl_txt_mv |
α- e β-pineno sÃo monoterpenos constituintes do Ãleo essencial de plantas encontradas no Nordeste do Brasil como a malva-santa e o eucalipto que, na medicina popular, sÃo usadas no tratamento de distÃrbios intestinais e respiratÃrios. As aÃÃes miorrelaxantes desses Ãleos essenciais sÃo atribuÃdas à presenÃa de α- e de β-pineno. Nosso objetivo foi estudar mais detalhadamente os efeitos desses constituintes sobre a contratilidade do mÃsculo liso gastrintestinal e sobre o esvaziamento gÃstrico de lÃquido em ratos. No presente estudo, foram usados ratos Wistar machos (200-250g) sacrificados por deslocamento cervical. Tiras de duodeno, Ãleo e fundo de estÃmago foram cortados e mantidos em Tyrode. As contraÃÃes isomÃtricas foram registradas atravÃs de transdutores de forÃa conectados a sistema computadorizado. SoluÃÃes contendo α- ou β-pineno foram preparadas em Tween 80 (concentraÃÃo final ≤ 0,2% v/v). Usados isoladamente, α- e β-pineno diminuÃram o tÃnus basal em duodeno com CI50 de 655,1 e 810,2 ÂM, respectivamente. ContraÃÃes submaximais induzidas por K+ (60 mM, K60) ou acetilcolina (ACh, 3 ÂM) foram inibidas, de maneira concentraÃÃo-dependente (p < 0,001, ANOVA), com valores de CI50 correspondentes a 790,0 [580,2-1007,4] e 760,0 [650,6-870,8] ÂM, respectivamente, para o α-pineno e 770,1 [500,3-1180,5] e 620,7 [520,9-750,2] ÂM para o β-pineno, respectivamente. Em preparaÃÃes prÃ-tratadas com 1 mM de α- ou β-pineno, a contraÃÃo fÃsica induzida por ACh (3 ÂM) em meio sem Ca2+ contendo EGTA (0,2 mM) foi reduzida de 18,4  3,3 % para 7,7  1,5 % e 5,0  1,2 % da contraÃÃo K60, respectivamente. A contraÃÃo tÃnica induzida por adiÃÃo de Ca2+ (2 mM) em preparaÃÃes mantidas na presenÃa de K+ (60 mM) ou ACh (3 ÂM), em meio sem Ca2+ contendo EGTA (0,2 mM), foi reduzida de 50,2  3,3 % e de 53,9  5,2 % para 10,6  2,6 % e 24,4  4,1 % pelo α-pineno e 6,6  1,1 % e 10,9  3,5 % pelo β-pineno, respectivamente. Em preparaÃÃes prÃ-tratadas com 1 mM de α- ou β-pineno, a contraÃÃo tÃnica induzida por ACh (60 ÂM) em Tyrode normal contendo verapamil (3 ÂM) foi reduzida de 29,0  4,1 % para 10,6  2,7 % e 12,5  2,2 % da K60, respectivamente. A resposta contrÃtil induzida pela cafeÃna (20 mM) em Tyrode normal foi potencializada de 47,8  3,2 % para 72,1  9,0 e 88,8  10,6 % da resposta controle pelo prÃ-tratamento da preparaÃÃo com α- ou β-pineno, respectivamente. Em meio sem Ca2+ com EGTA, a resposta contrÃtil da cafeÃna (20 mM) foi reduzida para 9,5  3,5 %. Sob essa condiÃÃo e, na presenÃa de α- ou β-pineno, a resposta nÃo foi alterada significativamente, correspondendo a 7,2  2,2 e 4,7  1,3 %, respectivamente. ApÃs esgotamento dos estoques intracelulares com CCh (100 mM), a contraÃÃo induzida por adiÃÃo de Ca2+ (2 mM), em meio sem Ca2+ com EGTA (0,2 mM) e verapamil (3 ÂM), foi potencializada pela adiÃÃo prÃvia de α- ou β-pineno de 30,7  2,1 % para 80,6  4,7 e 51,3  7,6 %, respectivamente (p < 0,05, teste de Bonferroni). Em estudos de retenÃÃo fracional de corante no trato gastrintestinal, o α- e o β-pineno aumentaram o esvaziamento gÃstrico, porÃm, a contratilidade induzida por ACh (3 ÂM) em tiras de fundo de estÃmago in vitro nÃo foi alterada pela presenÃa prÃvia de α- e β-pineno. O presente trabalho demonstra, pela primeira vez, que os monoterpenos α- e β-pineno apresentam efeito procinÃtico em ratos. Em tecidos isolados, nÃo afetam a contraÃÃo colinÃrgica em tiras de estÃmago, mas apresentam atividade miorrelaxante em tecido duodenal, por provÃvel interferÃncia com os mecanismos celulares mediados pela formaÃÃo de IP3. AlÃm disso, como demonstrado em Ãleo de rato, esses monoterpenos provavelmente ativam as vias de entrada de Ca2+ para a cÃlula em situaÃÃes de depleÃÃo dos estoques intracelulares |
| description |
The monoterpenes α- and β-pinene are constituents commonly found in several essential oils obtained from plants in Brazilian northeast such as âmalva-santaâ and âeucaliptoâ, which are used in folk medicine to treat respiratory and gastrointestinal dysfunctions. Myorelaxant actions are due to the presence of these constituents in their essential oils. The present work aimed to further study the pharmacological effects of these compounds on smooth muscle gastrointestinal contractility as well as on liquid gastric emptying in rats. Wistar rats (200-250 g) were used, sacrificed by cervical dislocation. Strips were carefully obtained from gastric fundus, duodenum and ileum, and were maintained in Tyrodeâs solution. Isometric contractions were recorded through force transducers coupled to a computerized data acquisition system. Solutions containing α- or β-pinene were prepared with Tween 80 (final concentration ≤ 0,2% v/v). Solely used, α- or β-pinene decreased duodenal basal tonus with IC50 value corresponding to 655.1 ÂM and 810.2 ÂM, respectively. Submaximal contractions induced by K+ (60 mM, K60) or acetylcholine (ACh, 3 ÂM) were inhibited, in a concentration-dependent manner (p < 0.001, ANOVA), with IC50 values of 790.0 [580.2-1007.4] e 760.0 [650.6-870.8] ÂM, respectively to α-pinene and 770.1 [500.3-1180.5] e 620.7 [520.9-750.2] ÂM, respectively to β-pinene. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM) in medium without Ca2+ with EGTA (0.2 mM), ACh (3 ÂM)-induced phasic contractions were inhibited from 18.4 Â 3.3% to 7.7 Â 1.5% and 5.0 Â 1.2% of K60, respectively. In tissues maintained under Ca2+-free conditions (in medium containing EGTA 0.2 mM) and in presence of K+ (60 mM) or ACh (3 ÂM), tonic contractions induced by Ca2+ addition were reduced from 50.2 Â 3.3% and 53.9 Â 5.2%, respectively to values corresponding to 10.6 Â 2.6 % and 24.4 Â 4.1 % to experiments with α-pinene and 6.6 Â 1.1 % and 10.9 Â 3.5 % to experiments with β-pinene, respectively. In tissues pre-treated with α- (1 mM) or β-pinene (1 mM), ACh (60 ÂM)-induced tonic contractions, in verapamil (3 ÂM)-containing medium, were inhibited from 29.0 Â 4.1 % to 10.6 Â 2.7 % and 12.5 Â 2.2 % of the K60, respectively. The caffeine (20 mM)-induced contractile response in normal Tyrodeâs solution was potentiated from 47.8 Â 3.2 % to 72.1 Â 9.0 and 88.8 Â 10.6 % of the control response in virtue of α- (1 mM) or β-pinene (1 mM) presence, respectively. In EGTA-containing Ca2+-free medium, the contractile response to caffeine was reduced to 9.5 Â 3.5%. Under these conditions, and in presence of α- (1 mM) or β-pinene (1 mM), this response was not significantly altered, with values corresponding to 7.2 Â 2.2 e 4.7 Â 1.3 %, respectively. In verapamil- and EGTA-containing Ca2+-free medium, after depletion of the intracellular Ca2+ stores by CCh (100 ÂM), the contractions induced by Ca2+ addition were potentiated by the presence of α- (1 mM) or β-pinene (1 mM) from 30.7 Â 2.1 % to 80.6 Â 4.7 and 51.3 Â 7.6 %, respectively (p < 0.05, Bonferroniâs test). In gastrointestinal dye fractional retention studies, α- or β-pinene increased the rat liquid gastric emptying. On the other hand, they did not alter the ACh-induced contractions on gastric fundus strips. Our study firstly shows that, both α- and β-pinene have prokinetic properties in rats. In isolated tissues, they did not affect cholinergic contractions on gastric fundus strips, but are myorelaxant compounds on rat duodenal preparations, probably by an interference with cellular mechanisms mediated by IP3 release. Moreover, α- and β-pinene activate capacitative Ca2+ entry to intracellular milieu after Ca2+ stores depletion |
| publishDate |
2007 |
| dc.date.issued.fl_str_mv |
2007-07-20 |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
| status_str |
publishedVersion |
| format |
masterThesis |
| dc.identifier.uri.fl_str_mv |
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1114 |
| url |
http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=1114 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Universidade Federal do Cearà |
| dc.publisher.program.fl_str_mv |
Programa de PÃs-GraduaÃÃo em Farmacologia |
| dc.publisher.initials.fl_str_mv |
UFC |
| dc.publisher.country.fl_str_mv |
BR |
| publisher.none.fl_str_mv |
Universidade Federal do Cearà |
| dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UFC instname:Universidade Federal do Ceará instacron:UFC |
| reponame_str |
Biblioteca Digital de Teses e Dissertações da UFC |
| collection |
Biblioteca Digital de Teses e Dissertações da UFC |
| instname_str |
Universidade Federal do Ceará |
| instacron_str |
UFC |
| institution |
UFC |
| repository.name.fl_str_mv |
-
|
| repository.mail.fl_str_mv |
mail@mail.com |
| _version_ |
1643295116957319168 |