Influences of Indomethacin on Contractions Induced by Endothelins in Guinea Pig Isolated Gallbladder
| Autor: | Giles A. Rae, Alcı́bia M Cardozo, Pedro D'Orléans-Juste, Hugo C. Nora |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.hormone
Male medicine.medical_specialty Guinea Pigs Indomethacin Peptide hormone In Vitro Techniques Peptides Cyclic Guinea pig Endothelins Indometacin Piperidines Internal medicine medicine Animals Receptor Pharmacology Chemistry Receptors Endothelin Gallbladder Receptor Endothelin A Receptor Endothelin B Endocrinology Eicosanoid cardiovascular system Female medicine.symptom Endothelin receptor Cardiology and Cardiovascular Medicine Oligopeptides medicine.drug Muscle contraction Muscle Contraction |
| Zdroj: | Journal of Cardiovascular Pharmacology. 36:S267-S269 |
| ISSN: | 0160-2446 |
| DOI: | 10.1097/00005344-200036001-00079 |
| Popis: | Endothelins (ETs) potently contract guinea pig gallbladder (GPGB) via endothelin-A and -B (ETA and ETB) receptors. This study assesses the possible participation of eicosanoids in the mediation of responses of the GPGB (Krebs' solution, 37 degrees C, 0.5 g load) triggered through each receptor type. Indomethacin (INDO; 5.6 microM) shifted the curve to endothelin-1 (ET-1) (0.1-100 nM) to the right, enhancing the CK50 (concentration causing 50% of response to KCl 80 mM) from 0.9 to 6.8 nM and reducing its EH (response to 100 nM) from 170 +/- 13 to 123 +/- 9 (% of response to 80mM KCl). INDO strongly depressed responses to sarafotoxin S6c (S6c; control CK50 0.9 nM), reducing its EH from 108 +/- 5 to 21 +/- 4. Neither BQ-123 nor BQ-788 (1 microM) changed responses to ET-1, but each markedly reduced responsiveness to ET-3 (control: CK50 of 9.7 nM and EH of 153 +/- 14; BQ-123: approximately = 100 nM and 44 +/- 12; BQ-788 approximately = 100 nM and 65 +/- 18). In the presence of BQ-123, INDO further depressed responses to ET-3 (EH 26 +/- 6), whereas in the presence of BQ-788, such responses were strongly enhanced (EH 126 +/- 9). These findings strongly suggest that contractions of GPGB caused via ETB receptors are mediated to a large extent by contractile eicosanoids, whereas those caused (at least by ET-3) via ETA receptors are limited by relaxant eicosanoids. The cellular sources and nature of the eicosanoids released by ETs remain to be established. |
| Databáze: | OpenAIRE |
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