title: ETB2 receptor subtype stimulation relaxes the iris sphincter muscle.
abstract: Effects of ET(B) receptor stimulation and its subcellular pathways were evaluated in carbachol pre-contracted rabbit iris sphincter muscles (n=51). ET(B) stimulation with sarafotoxin (SRTX-c; 10(-10)-10(-6) M) was tested in the absence (n=7) or presence of 10(-5) M of: BQ-788 (ET(B2) receptor antagonist; n=6), L-NA (NOS inhibitor; n=7) or indomethacin (cyclooxygenase inhibitor; n=10). Effects of ET(B) stimulation by endothelin-1 (ET-1; 10(-10)-10(-7) M) in the presence of an ET(A) receptor antagonist (BQ-123; 10(-5) M; n=7) and of ET(B1) stimulation by IRL-1620 (10(-10)-10(-7) M; n=7) were also tested. Finally, the effects of SRTX-c (10(-9)-10(-7) M) in electric field stimulation (EFS) contraction were evaluated (n=7). ET(B) receptor stimulation by SRTX-c or ET-1 in presence of BQ-123 promoted a concentration-dependent relaxation of the rabbit iris sphincter muscle by 10.8+/-2.0% and 9.4+/-1.8%, respectively. This effect was blocked by BQ-788 (-2.3+/-2.0 %), L-NA (4.5+/-2.3 %) or indomethacin (2.3+/-2.9 %). Selective ET(B1) stimulation by IRL-1620 did not relax the iris sphincter muscle (0.9+/-5.4 %). EFS elicited contraction was not altered by SRTX-c. In conclusion, ET(B) receptor stimulation relaxes the carbachol precontracted iris sphincter muscle, an effect that is mediated by the ET(B2) receptor subtype, through NO and the release of prostaglandins.
authors.affiliation: A. Rocha-Sousa, Department of Physiology, Faculty of Medicine, Porto, Portugal. arsousa@med.up.pt
authors.forename: A
authors.initials: A
authors.lastname: Rocha-Sousa
authors.forename: J
authors.initials: J
authors.lastname: Saraiva
authors.forename: M
authors.initials: M
authors.lastname: Amaral
authors.forename: P
authors.initials: P
authors.lastname: Alves-Faria
authors.forename: F
authors.initials: F
authors.lastname: Falcão-Reis
authors.forename: A F
authors.initials: AF
authors.lastname: Leite-Moreira
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D019332:Endothelin-1 / Q000378:metabolism*; D016232:Endothelins / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007498:Iris / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D011817:Rabbits; D044022:Receptor, Endothelin A / Q000378:metabolism; D044023:Receptor, Endothelin B / Q000819:agonists / Q000378:metabolism*; D014757:Viper Venoms
chemical_list: D019332:Endothelin-1; D016232:Endothelins; D004791:Enzyme Inhibitors; D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D010880:Piperidines; D011453:Prostaglandins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D014757:Viper Venoms; C089502:sarafotoxin-c; C074308:sovateltide; D019335:Nitroarginine; D009569:Nitric Oxide; C086539:BQ 788; D002217:Carbachol; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D007213:Indomethacin