title: Pre- and postjunctional actions of endothelin in the rat iris sphincter preparation.
abstract: Effects of endothelins (ETs) were studied in the rat iris sphincter preparation. Three peptides (ET-1, ET-2 and ET-3) caused contractile responses, and the rank order of agonist potency was: ET-1 = ET-2 > ET-3. The concentration-response curve to ET-1 was shifted to the right by the ETA receptor antagonist cyclo [D-Asp-L-Pro-D-Val-L-Leu-D-Trp] (BQ-123: 10(-7) M), the pA2 value of which was 7.41 +/- 0.09 (n = 4). ET-1 and ET-3, at the concentration of 10(-9) M, potentiated cholinergic contractions evoked by electrical field stimulation (5 and 20 Hz) without affecting the postjunctional sensitivity to carbachol. This potentiating effect was not influenced by BQ-123 (10(-6) M). The ET-evoked percentage increase in the stimulation-induced contraction observed at 5 Hz was significantly greater than that at 20 Hz. A release of immunoreactive ET was detected when the preparation was stimulated at 20 Hz (1.81 +/- 0.36 pg/sphincter n = 6). ET release evoked by 20 Hz stimulation was completely abolished by tetrodotoxin (10(-7) M). In conclusion, ET interacts with two different receptor types, ETA and non-ETA receptors (probably ETB) which exist post- and presynaptically at cholinergic neuroeffector junctions of the rat iris preparation. Stimulation of ETA receptor results in a direct muscle contraction and non-ETA receptor activation facilitates the acetylcholine output from cholinergic nerve endings. It is suggested that ET released from a tetrodotoxin-sensitive site is involved in the modulation of acetylcholine release in the rat iris sphincter preparation.
authors.affiliation: Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shinkai
authors.forename: H
authors.initials: H
authors.lastname: Tsuruoka
authors.forename: S
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: I
authors.initials: I
authors.lastname: Takayanagi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000145:classification / Q000494:pharmacology*; D066298:In Vitro Techniques; D007498:Iris / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)