Interaction of Opiate Peptides with Dopamine Effects on Prolactin Secretion and Membrane Electrical Properties in Anterior Pituitary Cells from Lactating Rats

Abstract

Met-enkephalin and b-endorphin induced a partial reversion of the dopamine inhibition of prolactin release from pituitary cells of lactating rats in primary culture. This effect of opiate peptides was dose-dependent with an EC50 of 40f8 nM and 4 5 + 7 nM and maximal blockade of dopamine inhibition of 60% and 68% for Met-enkephalin and /]-endorphin, respectively. Naloxone antagonized the effect of Met-enkephalin with an EC50 of 22_$12 nM. Furthermore, this Met-enkephalin effect on dopamine inhibition of prolactin secretion appeared non-competitive since it reduced maximal inhibition without affecting the apparent affinity of dopamine. Finally, it should be noted that the two opiate peptides had no effect on spontaneous prolactin release.In electrophysiological experiments, local ejection of dopamine on tested cells induced an hyperpolarization concomitant with an increase of the membrane conductance. Ejection of Met-enkephalin or /&endorphin alone did not modify the electrical properties of the cells (resting potential, membrane conductance and excitability). In contrast, both peptides blocked in a reversible manner the dopamine-induced electrical responses. These effects were antagonized by naloxone. However, this interaction of opiate peptides with dopamine electrical response was not observed on all cells tested. We conclude that the blocking effect of opiates on dopamine-induced hyperpolarization may account, at least in part, for the ability of these peptides to interact with dopamine inhibition of prolactin release.Prolactin (PRL) release is under a tonic inhibitory control by dopamine (DA) (1). Opiates have been shown to interact with DA inhibition of PRL secretion both at the hypothalamic (2-4) and pituitary level (5 -8). I n the anterior pituitary, morphine and opiate peptides had no effect on the spontaneous PRL release (9, 10) but reversed inhibition of secretion induced by DA. Although this was not observed under all experimental conditions (1 l), this effect seems to involve a specific opiate receptor since it has been shown to be blocked by opiate antagonists ( 5 , 6, 8). In addition, spccific opiate binding sites have been described in anterior pituitary membranes (12, 13), although they could not be fully characterized because of the important contamination of endogenous B-endorphin-like peptides (14).Recently, it has been shown that DA induced a hyperpolarizing response due to a n increased potassium conductance on human (1 S), bovine (16) and rat lactotrophs ( I 7). During this response spontaneous calcium action potentials were suppressed (17). DA was also shown to affect calcium and potassium fluxes in those cells (18). These phenomena are likely to be implicated in the mechanism o f action of DA on PRL release since, in addition to cyclic AMP (CAMP) production (19-22) and modulation of phosphatidylinositol phosphate breakdown (23-26), regulation of PRL secretion is dependent on calcium entry into lactotrophs (27,28).An effect of morphinomimetic peptides on the DA hyperpolarization of ...

Plasticity of the Prolactin (PRL) Axis: Mechanisms Underlying Regulation of Output in Female Mice

“…Previous studies have reported a change in the characteristics of these neurons in lactating rodents, with detection of increased opioidergic immunoreactivity in the arcuate nucleus [131,132] and specific expression of enkephalin (Enk) in TIDA neurons. Positive effects of endogenous opioids on PRL secretion have been described [133], which could result from inhibition of TIDA neurons themselves via suppression of DA turnover [134] or TH activity [135]. Thus, a role for Enk may be to reinforce the suppression of DA secretion from TIDA neurons, although as there are numerous other targets for opioids within the hypothalamus, as well as other regions of the brain [136], it is tempting to speculate that Enk may instead modify secretion of potential PRL-releasing factors.…”