A D-2 dopaminergic agonist stimulates secretion of anterior pituitary immunoreactive beta-endorphin in rats.
Hypothalamic dopamine neurons are known to control circulating levels of immunoreactive beta-endorphin (i beta-END) by inhibiting hormone secretion by the intermediate lobe (IL) of the pituitary gland. We examined the ability of the D-2 selective dopaminergic agonist, LY141865, to influence circulating levels of i beta-END in rats and found that in contrast to inhibiting IL secretion, LY141865 increased release of i beta-END from the anterior lobe (AL). Intraperitoneal injection of 1 mg/kg LY141865 transiently increased plasma levels of i beta-END by 7-30 min after drug treatment; plasma prolactin levels were maximally reduced within 15 min and throughout the remaining 2-hour time course of treatment. Doses of 0.3 and 1.0 mg/kg of LY141865 increased circulating i beta-END to 440 and 690%, respectively, of control levels (0.38 +/- 0.12 ng/ml, mean +/- SEM, n = 6). Lower doses of the D-2 agonist (0.01-0.1 mg/kg) failed to significantly affect plasma i beta-END. Sephadex G-50 chromatography of plasma pools revealed that virtually all of the increase due to LY141865 treatment was immunoreactivity resembling beta-lipotropin in molecular size, the principal component of AL secretion of i beta-END. Furthermore, LY141865-evoked release was blocked by pretreatment of rats with dexamethasone (50 micrograms/kg i.p., 4 h) which inhibits AL but not IL secretion of pro-opiomelanocortin-derived peptides. Stimulation of i beta-END release by LY141865 was also inhibited by the general dopamine antagonist, haloperidol, (0.1-3.0 mg/kg i.p., 2 h) and by the D-2 selective antagonist, sulpiride (100 micrograms/rat i.c.v., 4 h).(ABSTRACT TRUNCATED AT 250 WORDS)
Farah
J M
JM
Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, Md.
Mueller
G P
GP
D000818:Animals; D002850:Chromatography, Gel; D046508:Culture Techniques; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000097:blood; D019257:Quinpirole; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D013997:Time Factors; D001615:beta-Endorphin / Q000276:immunology / Q000378:metabolism*
D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D019257:Quinpirole; D001615:beta-Endorphin; D011388:Prolactin; D006220:Haloperidol