Peripheral cholecystokinin type A receptors mediate oxytocin secretion in vivo.
Cholecystokinin-octapeptide (CCK8) administered intraperitoneally (i.p.) in rats induces a rapid elevation in serum oxytocin (OT). The receptor subtype mediating this action of CCK was investigated with selective CCK-A and CCK-B receptor agonists and antagonists. CCK8 and A-71623, a potent CCK-A selective agonist, were similar in efficacy and potency for stimulating OT secretion. Both compounds at 10 nmol/kg elicited approximately one-half the response of 100 nmol/kg, which elevated serum OT to approx. 20 to 30-fold above basal level. The potent CCK-B selective agonist, A-63387, at doses up to 100 nmol/kg did not increase serum OT. MK-329, a CCK-A receptor selective antagonist, at a dose of 20 nmol/kg fully inhibited the action of 20 nmol/kg CCK8, while 100 nmol/kg of (R)L-365,260, a CCK-B selective antagonist, had no effect on the CCK8 response. These results, together with previous lesion studies, suggest that vagal CCK-A receptors in the periphery mediate the activation of the oxytocinergic pathway in vivo.
Miller
T R
TR
Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, IL 60064.
Bianchi
B R
BR
Witte
D G
DG
Lin
C W
CW
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors; D020109:Devazepide; D007274:Injections, Intraperitoneal; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D010121:Oxytocin / Q000097:blood*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide / Q000008:administration & dosage / Q000494:pharmacology; D013758:Tetragastrin / Q000031:analogs & derivatives / Q000494:pharmacology
D001570:Benzodiazepinones; D009842:Oligopeptides; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; C066278:A 71623; C075264:A 63387; D010121:Oxytocin; D002766:Cholecystokinin; D020109:Devazepide; D012844:Sincalide