A D-2 Dopaminergic Agonist Stimulates Secretion of Anterior Pituitary Immunoreactive β-Endorphin in Rats

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Abstract
Hypothalamic dopamine neurons are known to control circulating levels of immunoreactive β-endorphin (iβ-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 iβ-END in rats and found that in contrast to inhibiting IL secretion, LY141865 increased release of iβ-END from the anterior lobe (AL). Intraperitoneal injection of 1 mg/kg LY141865 transiently increased plasma levels of iβ-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 iβ-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 iβ-END. Sephadex G-50 chromatography of plasma pools revealed that virtually all of the increase due to LY141865 treatment was immunoreactivity resembling β-lipotropin in molecular size, the principal component of AL secretion of iβ-END. Furthermore, LY141865-evoked release was blocked by pretreatment of rats with dexamethasone (50 µg/kg i.p., 4 h) which inhibits AL but not IL secretion of pro-opiomelanocortin-derived peptides. Stimulation of iβ-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, sulphide (100 µg/rat i.c.v., 4 h). These results indicate that the effects of LY141865 treatment on pituitary release of iβ-END are mediated by dopaminergic receptor activation, probably of the D-2 type, within the central nervous system. Since neither dopamine nor LY141865 directly influences AL secretion of iβ-END, the effects of D-2 receptor stimulation in vivo are probably mediated by actions of LY141865 on secretion of hypothalamic corticotropin-releasing factor, the principal physiologic stimulator of hormone secretion from pituitary corticotrophs.