Adenosine acts by A1 receptors to stimulate release of prolactin from anterior-pituitaries in vitro.
Adenosine has been identified in the anterior pituitary gland and is secreted from cultured folliculostellate (FS) cells. To determine whether adenosine controls the secretion of anterior pituitary hormones in vitro, adenosine was incubated with anterior pituitaries. It stimulated prolactin (PRL) release at the lowest concentration used (10(-10) M); the stimulation peaked at 10(-8) M with a threefold increase in release and declined to minimal stimulation at 10(-4) and 10(-3) M. Follicle-stimulating hormone release was maximally inhibited at 10(-8) M, whereas luteinizing hormone release was not significantly inhibited. Two selective A1 adenosine receptor antagonists (10(-7) or 10(-5) M) had no effect on basal PRL release, but either antagonist completely blocked the response to the most effective concentration of adenosine (10(-8) M). In contrast, a highly specific A2 receptor antagonist (10(-7) or 10(-5) M) had no effect on basal PRL release or the stimulation of PRL release induced by adenosine (10(-8) M). We conclude that adenosine acts to stimulate PRL release in vitro by activating A1 receptors. Since the A1 receptors decrease intracellular-free calcium, this would decrease the activation of nitric oxide synthase in the FS cells, resulting in decreased release of nitric oxide (NO). NO inhibits PRL release by activating guanylate cyclase that synthesizes cGMP from GTP; cGMP concentrations increase in the lactotrophs leading to inhibition of PRL release. In the case of adenosine, NO release from the FS cells decreases, resulting in decreased concentrations of NO in the lactotrophs, consequent decreased cGMP formation, and resultant increased PRL release.
Yu
W H
WH
Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Road, Baton Rouge, LA 70808-4124, USA.
Kimura
M
M
Walczewska
A
A
Porter
J C
JC
McCann
S M
SM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D058915:Purinergic P1 Receptor Antagonists; D043705:Receptor, Adenosine A2A; D018047:Receptors, Purinergic P1; C053907:8-cyclopentyl-1,3-dimethylxanthine; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine