L-type calcium channels and CRH-mediated ACTH and cortisol release in humans.
1. The effect of pretreatment with nifedipine on naloxone-stimulated corticotrophin-releasing hormone (CRH)-induced adrenocorticotrophin (ACTH) release in humans was investigated. The mean peak plasma ACTH and cortisol levels and the mean peak change in cortisol levels from basal were significantly lower in the nifedipine/naloxone test than in the naloxone alone test. The integrated areas under the ACTH-time and cortisol-time curves were reduced by 33 and 49%, respectively, in the nifedipine/naloxone test compared with the naloxone alone test. These results correlate well with published in vitro studies. 2. Acute administration of oral nifedipine partially inhibited naloxone-stimulated ACTH and cortisol release, probably by blockade of plasma membrane voltage-dependent L-type calcium channels normally activated following binding of CRH to pituitary corticotroph receptors. 3. Naloxone-induced CRH release may replace insulin hypoglycaemia testing of pituitary ACTH reserve in humans.
Hockings
G I
GI
University Department of Medicine, Greenslopes Hospital, Brisbane, Queensland, Australia.
Grice
J E
JE
Walters
M M
MM
Jackson
R V
RV
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000328:Adult; D015220:Calcium Channels / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D016037:Single-Blind Method; D013997:Time Factors
D015220:Calcium Channels; D009270:Naloxone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D009543:Nifedipine; D006854:Hydrocortisone