In vivo and in vitro effects of arginine-vasopressin receptor antagonists on the hypothalamic-pituitary-adrenal axis in the rat.
Arginine-vasopressin (AVP) is regarded as a potent stimulator of pituitary adrenocorticotropin (ACTH) secretion and participates therefore in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis function in concert with the physiological activator of the axis, hypothalamic corticotropin-releasing hormone (CRH). We examined the effects of AVP and/or three synthetic V1b receptor antagonists on the activity of the HPA axis in vivo and in vitro in the rat. AVP was injected intravenously to Sprague-Dawley rats (1 microgram/rat) through an indwelling jugular catheter. AVP stimulated ACTH release, with maximal effect 10 min after injection. Intravenous injection of three V1b antagonists, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin (d(CH2)5[Tyr(Et2)]VAVP (WK 1-1), 9-desglycine[1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid), 2-O-ethyltyrosine, 4-valine] arginine vasopressin desGly9d(CH2)5 [Tyr(Et2)]-VAVP (WK 3-6), and 9-desglycine [1-(beta-mercapto-beta,beta- cyclopentamethylenepropionic acid),2-D-(O-ethyl)tyrosine, 4-valine ] arginine vasopressin des Gly9d(CH2)5[D-Tyr(Et2)]VAVP (AO 3-21), prevented AVP-stimulated ACTH secretion. Explanted rat hypothalami incubated in vitro with graded concentrations of AVP (10(-14)-10(-5) M) secreted immunoreactive CRH (iCRH) in a concentration-dependent fashion. Maximal stimulatory effect occurred at the concentration of 10(-6) M. Incubation of hypothalami with WK 1-1, WK3-6, or AO 3-21 (10(-6) M) prevented AVP-stimulated iCRH secretion. Results suggest that AVP plays a relevant, multiple role in the activation of the HPA axis in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Developmental Endocrinology Branch, NICHD, NIH, Bethesda, Md.
R
R
Bernardini
A
A
Chiarenza
T C
TC
Kamilaris
N
N
Renaud
L
L
Lempereur
M
M
Demitrack
P W
PW
Gold
G P
GP
Chrousos
D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin; C015981:argipressin,beta-mercapto-beta,beta-cyclopentamethylenepropionic acid(1)-Val(4)-; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; C050890:1-((beta-mercapto-beta)beta cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-9-des-Gly-arginine vasopressin