Stimulatory effects of adenosine on prolactin secretion in the pituitary gland of the rat

Abstract

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 µM) 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.

Adenosine A1 receptor-mediated inhibition of in vitro prolactin secretion from the rat anterior pituitary

“…The doses of 1 and 10 µM caused a decrease that was lower than the maximum inhibition produced by the 0.1-µM dose (Figure 2), indicating a biphasic pattern of response (Ushaped dose-response curve). These results compare well with our earlier report of biphasic purinergic effects on PRL secretion stimulated by the adenosine agonist (A 2 > A 1 ) 5-(N-methylcarboxyamido)adenosine (MECA) (11). We showed that the 10 µM dose had only a residual stimulatory effect on PRL secretion in hemipituitaries incubated in vitro compared with 1 µM (maximum stimulatory response).…”

Prolactin in headache and migraine: A systematic review of clinical studies

“…Enhances PRL secretion in rodents [78]. patients with prolactinomas compared to nonfunctioning pituitary adenomas (54) and lowering PRL levels with D2 receptor agonist relieved headache in hyperprolactinemic patients (56).…”

Hemicrania Continua Secondary to an Ipsilateral Brainstem Lesion

“…In mice its half‐life in the serum and the brain was 10 and 24 hours, respectively, following indomethacin oral administration (2.4 times higher in cerebral tissue) 24 . Hypothetically indomethacin might attenuate the headache by acting on brain centers and peripheral pain‐related structures, simultaneously, throughout different mechanisms: (1) changing the secretory processes of prostaglandin, neurotransmitters, and neurohormones from brain tissues; 25,26 (2) altering pituitary hormonal secretion which may, in turn, directly or indirectly affect cerebral function; 27 (3) decreasing CBF via a vasoconstrictive effect; 28 and (4) exerting its anti‐inflammatory action.…”