Stimulatory effects of adenosine on prolactin secretion in the pituitary gland of the rat.
We investigated the effects of adenosine on prolactin (PRL) secretion from rat anterior pituitaries incubated in vitro. The administration of 5-N-methylcarboxamidoadenosine (MECA), an analog agonist that preferentially activates A2 receptors, induced a dose-dependent (1 nM to 1 microM) increase in the levels of PRL released, an effect abolished by 1,3-dipropyl-7-methylxanthine, an antagonist of A2 adenosine receptors. In addition, the basal levels of PRL secretion were decreased by the blockade of cyclooxygenase or lipoxygenase pathways, with indomethacin and nordihydroguaiaretic acid (NDGA), respectively. The stimulatory effects of MECA on PRL secretion persisted even after the addition of indomethacin, but not of NDGA, to the medium. MECA was unable to stimulate PRL secretion in the presence of dopamine, the strongest inhibitor of PRL release that works by inducing a decrease in adenylyl cyclase activity. Furthermore, the addition of adenosine (10 nM) mimicked the effects of MECA on PRL secretion, an effect that persisted regardless of the presence of LiCl (5 mM). The basal secretion of PRL was significatively reduced by LiCl, and restored by the concomitant addition of both LiCl and myo-inositol. These results indicate that PRL secretion is under a multifactorial regulatory mechanism, with the participation of different enzymes, including adenylyl cyclase, inositol-1-phosphatase, cyclooxygenase, and lipoxygenase. However, the increase in PRL secretion observed in the lactotroph in response to A2 adenosine receptor activation probably was mediated by mechanisms involving regulation of adenylyl cyclase, independent of membrane phosphoinositide synthesis or cyclooxygenase activity and partially dependent on lipoxygenase arachidonic acid-derived substances.
Departamento de Fisiologia, Centro de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brasil.
D L W
DL
Picanço-Diniz
M M
MM
Valenca
A L V
AL
Favaretto
J
J
Antunes-Rodrigues
D000241:Adenosine / Q000494:pharmacology*; D000262:Adenylyl Cyclases / Q000494:pharmacology; D000818:Animals; D008084:Lipoxygenase / Q000494:pharmacology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000502:physiology; D011388:Prolactin / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D011388:Prolactin; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D000262:Adenylyl Cyclases; D000241:Adenosine