Mu‐Selective Opioid Peptides Stimulate Prolactin Release in Lactating Rats

Abstract

The fact that opiates elicit prolactin secretion is well known. However, we have recently discovered that morphine does not stimulate prolactin release in lactating rats. The physiological basis for this alteration in opiate sensitivity during lactation is not known. Since morphine-induced prolactin secretion in male rats is mediated via the mu opioid receptor subtype, one possible explanation is that mi1 receptors are down-regulated during lactation. To address this possibility, the effects of mu opioid peptides on prolactin secretion were examined in lactating rats. The presumed mu-selective peptides DAGO ([D-Ala', Me-Phe4, Gly-01'1-enkephalin) and PLO-17 ("Me-Phe3, D-Pro4]-morphiceptin) were administered to primiparous lactating rats and the resulting hormone responses measured. Both DAGO and PLO-17 caused a rapid and significant rise in plasma prolactin during lactation. The prolactin-releasing effects of both peptides were naloxone reversible, suggesting involvement of opioid receptors. Moreover, the DAGO-induced secretion of prolactin could be completely abolished by pretreatment with the irreversible mu antagonist b-funaltrexamine. In lactating rats, DAGO and PLO-17 were poor growth hormone-releasing agents, providing further evidence for the mu specificity of these peptides. These results imply that during lactation, as in other reproductive states, mu opioid receptor sites are positively coupled to the prolactin secretory mechanism. Thus, the previously observed inability of morphine to elicit prolactin release in lactating rats cannot be explained on the basis of down-regulation of mu opioid receptors.The \timulatory effect of opioids on prolactin (PRL) release is well estaidished for several mammalian species, including man (1, 2). In tile rat, opioid antagonists such as naloxone, suppress basal and stimulus-induced PRL release suggesting that endogenous opiclid peptides (EOPs) may have an important role in the phqyiological regulation of PRL secretion (1, 2). Although most evidLmce points to central sites of EOP action (3-9, direct opioid effects at the level of the anterior pituitary cannot be completely m1eC out (6). Recently, the concept of multiple opioid receptors has gained wide acceptance, and many investigators have attempted to correlate specific neuroendocrine functions with particular opioid receptor subtypes (7-1 6).There is general agreement that at least three major opioid receptor populations are present: mu, kappa, and delta sites (17 19). The characterization of receptor subtypes is based largely on !he affinities of opioid ligands for particular binding sites in Vitvri Thus, morphine is the prototypical mu receptor agonist while enkephalin peptides interact preferentially with delta sites. Kelaocine-like drugs are potent, though non-selective, kappa agonists, and dynorphins appear to be the endogenous ligands for the kappa site (17,19). Unfortunately, determining the functional importance of specific opioid receptor subtypes has been difficult due to the fact that few opioid...

Participation of Opioid Peptides in Sucking-induced Oxytocin and Prolactin Secretions in Lactating Goats

“…They mostly show that EOP are involved in the regulation of PRL secretion during lactation and have a stimulatory action on sucking‐induced PRL release (Ferland et al. 1978; Selmanoff and Gregerson 1986; Baumann and Rabii 1990; Soaje et al. 2002).…”

“…Most of the studies on the central regulatory mechanisms controlling PRL secretion induced by sucking have been performed in rats. They mostly show that EOP are involved in the regulation of PRL secretion during lactation and have a stimulatory action on sucking-induced PRL release (Ferland et al 1978;Selmanoff and Gregerson 1986;Baumann and Rabii 1990;Soaje et al 2002). Mu-and kappa-receptor agonists stimulate PRL secretion and these effects are blocked by their respective antagonists (Krulich et al 1986a,b;Leadem and Yagenova 1987).…”

“…Most of the current knowledge on the central regulatory mechanisms controlling PRL and OT secretion induced by sucking comes from studies performed in rodents. In rats, endogenous opioid peptides (EOP) are involved in the regulation of PRL secretion during lactation (Baumann and Rabii 1990; Arbogast and Voogt 1998; Soaje et al. 2002).…”

Opioid system functional regulation in neurological disease management

“…μ‐Receptors are responsible for supraspinal analgesia, respiratory depression, euphoria, sedation, decreased gastrointestinal motility, and physical dependence. Subtypes include μ 1 and μ 2 , with μ 1 related to analgesia, euphoria, and serenity and μ 2 related to respiratory depression, pruritus, prolactin release, dependence, anorexia, and sedation (Baumann and Rabii, 1990; Vonhof and Sirén, 1991; Trescot et al, 2008). These receptors are also called OP3 or morphine opioid receptors (MOR).…”