Angiotensin II and ACTH release: site of action and potency relative to corticotropin releasing factor and vasopressin.
The present studies were designed to test, using a combination of in vivo and in vitro paradigms, the potency of angiotensin II (AII) to release ACTH, in relation to that of other neural peptides with corticotropin-releasing activity (CRA), such as synthetic corticotropin releasing factor (CRF), arginine vasopressin (AVP) and oxytocin (OXY); and to determine whether a central or peripheral locus is the primary site of action of the peptide. Injection of AII (1 and 5 micrograms, i.p.) in intact unanesthetized male rats, resulted in an increase in plasma ACTH and beta-endorphin-like immunoreactivity (beta-end-LI) levels after the largest dose. The responses, however, were not as pronounced as those elicited by 0.5 microgram of CRF or 1 micrograms of AVP. Injection of AII (i.v., 1 or 5 micrograms) in centrally blocked rats (pretreated with chlorpromazine-morphine-nembutal) failed to elicit any increase in either ACTH or bet a-end-LI levels, whereas 0.5 microgram of either CRF or AVP increased both hormones several fold. In vitro studies using dispersed anterior pituitary cells obtained from male donor rats showed that AII as well as AIII could increase ACTH release at doses of 10(-8) M or larger. Under the same conditions, CRF and AVP stimulated ACTH release to a greater degree at 10(-10) and 10(-9) M, respectively. On the other hand, OXY was stimulatory at 10(-8) M. Dose-response studies indicated a rank order of CRA as follows: CRF greater than AVP greater than OXY greater than AII = AIII. Both AII and AIII showed additive effects when coincubated with either CRF or AVP.(ABSTRACT TRUNCATED AT 250 WORDS)
D000324:Adrenocorticotropic Hormone / Q000032:analysis / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology*; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001681:Biological Assay; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004723:Endorphins / Q000032:analysis / Q000378:metabolism; D008297:Male; D010121:Oxytocin / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D012504:Saralasin / Q000494:pharmacology; D001615:beta-Endorphin
D004723:Endorphins; D010455:Peptides; D000804:Angiotensin II; D001127:Arginine Vasopressin; D000805:Angiotensin III; D010121:Oxytocin; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D012504:Saralasin