Kinetic Actions and Interactions of Arginine Vasopressin, Angiotensin-II, and Oxytocin on Adrenocorticotropin Secretion by Rat Anterior Pituitary Cells in the Microperifusion System*

Abstract

We have examined the actions and interactions of arginine vasopressin (AVP), angiotensin-II (AII), and oxytocin (OT) on the ACTH secretory response of dispersed rat anterior pituitary cells in a microperifusion system. There was a dose-dependent ACTH secretory response to a 3-min perifusion of AII which reached its maximum 10 sec after the cells were exposed to AII and fell rapidly to baseline within 2 min, despite continued infusion of AII. This brief spike type of pattern is similar to that produced by AVP, but different from the sustained plateau response induced by CRF. The threshold stimulating concentration of AII was about 10(-9) M; the maximally stimulating concentration was not defined, but was 10(-6) M or more. The initial ACTH response to OT was similar, but fell to a plateau 2 min after the cells were exposed to OT and remained constant until perifusion with OT was stopped, after which it fell rapidly to baseline. The threshold stimulating concentration of OT was 10(-8) M; the maximally stimulating concentration was not defined, but was 10(-6) M or more. The ACTH secretory response to 10(-8) M AII was greatly diminished when cells were exposed to 10(-6) AVP or 10(-6) M OT before AII infusion. However, prior exposure to AII had no effect on the magnitude of the ACTH secretory response to either AVP or OT. The effects of simultaneous perifusion of AII and AVP and of AII and OT were additive. When AVP and OT were perifused sequentially, the ACTH secretory response to the peptide that was infused second was completely abolished. Furthermore, the combination of AVP and OT stimulated no greater response than either agent alone. When cells were perifused with the combination of 10(-7) M OT and 10(-7)- to 10(-5)-M concentrations of two potent AVP V1 receptor antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]-Arg8-vasopressin and [1-deaminopenicillamine-2-(O-methyl)tyrosine]-Arg8-vasopressin, both phases of the response to OT were progressively and almost completely inhibited. The initial spike phase was inhibited at lower antagonist concentrations than the sustained plateau phase.(ABSTRACT TRUNCATED AT 400 WORDS)