Adenosine regulates the release of adrenocorticotropic hormone (ACTH) from cultured anterior pituitary cells.
We have recently shown the presence of adenosine receptors coupled to adenylate cyclase in anterior pituitary and in the present studies we have investigated the effects of adenosine on ACTH release. The 'R'-site specific analogs of adenosine such as N-Ethylcarboxamide adenosine (NECA), L-N6-phenylisopropyl adenosine (PIA), 2-chloro-adenosine (2-Cl-Ado) all stimulated ACTH release in a dose-dependent manner. NECA was the most potent analog and stimulated ACTH release by about 170% with an apparent Ka of 0.1 microM, whereas PIA and 2-Cl-Ado were less potent and stimulated the release by about 110% and 125% with an apparent Ka of 0.2 and 0.4 microM respectively. The stimulation of ACTH release by NECA was inhibited by 3-isobutyl-1-methylxanthine (IBMX). On the other hand, adenosine deaminase (ADA) treatment of the cells also stimulated ACTH release as well as adenylate cyclase activity by about 2-fold, suggesting that endogenous adenosine plays an inhibitory role in the release of ACTH. Other agents, such as corticotropin-releasing factor (CRF), vasoactive intestinal peptide (VIP) and forskolin (FSK) also stimulated ACTH release from these cells. In addition, the stimulation by an optimal concentration of NECA was almost additive with maximal stimulation caused by VIP and FSK. These data suggest that adenosine modulates ACTH release from anterior pituitary through its interaction with adenosine receptors coupled to adenylate cyclase.
Anand-Srivastava
M B
MB
Clinical Research Institute of Montreal, Quebec, Canada.
Cantin
M
M
Gutkowska
J
J
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D019830:Adenosine-5'-(N-ethylcarboxamide); D000262:Adenylyl Cyclases / Q000378:metabolism; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D005260:Female; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D005576:Colforsin; C008514:methylxanthine; D019830:Adenosine-5'-(N-ethylcarboxamide); D014660:Vasoactive Intestinal Peptide; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000262:Adenylyl Cyclases; D000241:Adenosine