Atrial natriuretic peptides inhibit the release of corticotrophin-releasing factor-41 from the rat hypothalamus in vitro.
Atrial natriuretic peptide, ANP(99-126), is derived from cardiac atrial tissue and has potent effects on salt and water homeostasis, including the inhibition of aldosterone and vasopressin release. Recent studies have also suggested that it may suppress the pituitary-adrenal axis. In addition, N-truncated forms of ANP, such as ANP(103-126), have been identified within the central nervous system, with a prominent hypothalamic localization in the paraventricular nucleus. We have therefore investigated whether ANP(99-126) and ANP(103-126) are able to modulate the release of the principal ACTH-releasing factor, corticotrophin-releasing factor-41 (CRF-41), from the rat hypothalamus in vitro. The static incubation system has been previously described in detail. Male Wistar rats were decapitated between 09.00 and 09.30 h, their hypothalami rapidly removed, and four half-hypothalami incubated for 20-min intervals following a period of stabilization. The effect of the ANP peptides on the basal (B) and KCl (28 mmol/l)-stimulated (S) release of immunoreactive CRF-41 was studied by means of successive incubations in the absence (B1, S1) and presence (B2, S2) of the peptides. The ratios B2:B1 and S2:S1 were compared with parallel control incubations by ANOVA. Neither form of ANP had any effect on the basal release of CRF-41. ANP(99-126) caused a dose-dependent inhibition of CRF-41 release in the concentration range 1-100 nmol (P less than 0.01). ANP(103-126) also suppressed the release of CRF-41 in the concentration range 100 pmol/l-100 nmol/l (P less than 0.01), with a minimum S2:S1 ratio at 10 nmol/l, and a decrease in effect at 100 nmol/l. Finally, the stimulation of CRF-41 release induced by noradrenaline (10 nmol/l and 1 mumol/l) was non-competitively antagonized by 100 nmol ANP(99-126)/l and 10 nmol ANP(103-126)/l.(ABSTRACT TRUNCATED AT 250 WORDS)
Ibanez-Santos
J
J
Department of Endocrinology, St Bartholomew's Hospital, London.
Tsagarakis
S
S
Rees
L H
LH
Besser
G M
GM
Grossman
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D010446:Peptide Fragments; C062525:atrial natriuretic factor prohormone (103-126); D009320:Atrial Natriuretic Factor; D003346:Corticotropin-Releasing Hormone