Pharmacological characterization of arginine vasotocin vascular smooth muscle receptors in the trout (Oncorhynchus mykiss) in vitro

Arginine vasotocin (AVT) is present in the neurohypophysis of all nonmammal ian vertebrates and it appears to be the antecedent. of the neurohypophysia l nonapeptide hormones. Relatively little is known about AVT receptors in l ower vertebrates, especially fish, and the present study was designed to ex amine AVT receptor interactions in trout vascular and nonvascular smooth mu scle in vitro. AVT produced dose-dependent contraction of isolated rings fr om celiacomesenteric, coronary, and efferent branchial arteries, ventral ao rta, anterior cardinal vein, and strips of ductus Cuvier. The greatest effi cacy (magnitude of contraction per unit tissue weight) and sensitivity (eff ective concentration for half-maximal response, EC50) to AVT was found in t he efferent bronchial artery (EBA) and its receptors were characterized fur ther. Other neurohypophysial peptides, including arginine vasopressin (AVP) , lysine vasopressin (LVP), isotocin (IST), and oxytocin (OXY), contracted EBA with an efficacy order of (most to least) AVT = AVP = OXY > LVP > IST a nd a sensitivity order of AVT > OXY greater than or equal to AVP > IST > LV P Neither Desmopressin, an AVP V-2-receptor agonist, nor the AVP ring fragm ent, AVP(4-9), contracted EBA nor did they inhibit AVT contraction. Pretrea tment of EBA rings with the selective AVP V-1-receptor antagonists (deamino -Pen(1), O-Me-Tyr(2), Arg(8)-vasopressin and deamino-Pen(1), Val(4), Arg(8) -vasopressin), the selective V-2-receptor antagonist (adamantaneacetyl(1), O-Et-D-Tyr(0), Val(4), aminobutyryl(6), Arg(8,9)-vasopressin), or the combi ned V-1-oxytocin receptor antagonist (d(CH2)(5)[Tyr(Me)(2), Orn(8)-AVT]) co mpetitively inhibited AVT contractions without affecting AVT efficacy. Rece ptor affinity constants (pA(2)) determined by Schild analysis were in the r ange of 6.8-7.3, with slightly higher constants for the AVP V-1-/oxytocin r eceptor antagonists than for the selective V-2-receptor antagonist. Endothe lium removal had no effect on EBA sensitivity to AVT. EBA rings were an ord er of magnitude more sensitive to AVT than nonvascular gastrointestinal and urinary bladder smooth muscle rings or strips. However, AVT (10(-7) M) was as efficacious as acetylcholine (10(-5) M) in gastrointestinal, gallbladde r, and urinary bladder smooth muscle. It is concluded that trout EBA posses s an AVT smooth muscle receptor that shares a similar pharmacological profi le with the mammalian vascular AVP V-1a-receptor and the OXY-receptor, but it is distinct from the previously reported gill epithelial cell receptor. (C) 1999 Academic Press.