Differential role of the opioid μ and δ receptors in the activation of prolactin (PRL) and growth hormone (GH) secretion by morphine in the male rat

Koenig, James I.; Mayfield, M.A.; McCann, Samuel M.; Krulich, L.

doi:10.1016/0024-3205(84)90676-3

Cited by 60 publications

(52 citation statements)

References 27 publications

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“…It is important to note that DAGO (18,19,26,33), PLO-I7 (27), and morphine (18,37) have all been classified as selective mu receptor agonists in vitro. However, as mentioned previously, PRL and G H release in response to morphine involves multiple opioid receptor mechanisms (8,9). Morphine stimulates G H secretion in male rats via activation of delta receptors, and is thus not a mu-selective ligand in vivo.…”

Section: Discussionmentioning

confidence: 90%

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Mu‐Selective Opioid Peptides Stimulate Prolactin Release in Lactating Rats

Baumann

Rabii

1990

J Neuroendocrinology

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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...

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Section: Discussionmentioning

confidence: 90%

“…In the rat, stimulation of PRL by morphine is mediated via the mu and/or mu, opioid receptor subtype(s) (8,9), while increased growth hormone (GH) release involves interaction at a non-mu site, possibly the delta subtype (9). Kappa agonists are also potent PRL-releasing agents in this species (13,14).…”

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confidence: 99%

Mu‐Selective Opioid Peptides Stimulate Prolactin Release in Lactating Rats

Baumann

Rabii

1990

J Neuroendocrinology

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“…Ligands which are not mu-selective also can activate PRL release but by interacting with the low affinity mu-2 receptor or, activate the epsilon receptor, in the case of betaendorphin. The GH response does not appear to involve a mu-type receptor (39).…”

Section: Regulation Of Prolactin Secretionmentioning

confidence: 88%

Pituitary Gland: Neuropeptides, Neurotransmitters and Growth Factors

Koenig

1989

Toxicol Pathol

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ABSTIZACXThe hypothalamus receives neuronal afferents from numerous sources including inputs from limbic structures, such as the amygdala and hippocampus, and from brainstem regions involved in the regulation of the cardiovascular system and other autonomic functions. These afferents using a vast array of neurotransmitters and neuropeptides influence the activity of the hypothalamic neurons which synthesize and secrete the hypothalamic releasing and release-inhibiting factors into the hypophyseal portal circulatory system. The afferents can modulate the activity of the hypothalamic neurons by forming synapses on the neuronal cell body, on the nerve terminals in the median eminence or both. The chemicals most frequently used as neurotransmitters are the biogenic amines, including the catecholamines (norepinephrine, dopamine and epinephrine), serotonin, acetylcholine and gamma-aminobutyric acid (GABA). The stirnulatory influence of norepinephrine, serotonin, and acetylcholine on the secretion of corticotropin (ACTH) in rodents and man will be discussed, whereas GABA exerts an inhibitory effect on the secretion of ACTH in both man and rodents. These effects appear to be mediated by changes in the secretion of the corticotropin-releasing hormone (CRH) and vasopressin into the hypophyseal portal circulation. Numerous neuropeptides appear to alter the secretion of ACTH in the rat. We will discuss the stirnulatory actions of neuropeptide Y (NPY), angiotensin 11, and peptides of immune cell origin on the secretion of ACTH and CRH. The opioid peptides inhibit the secretion of CRH into the portal blood, however, they exert a potent stirnulatory effect on prolactin secretion in the rat and man. We will discuss the receptor subtypes involved in mediating these effects and the interactions of the opioid peptides with the neurotransmitter-containing neurons which project to the hypothalamus. This discussion will focus on the factors which impinge on the releasing factor-containingneurons in the hypothalamus and how they can be studied under in viso and in vitro conditions.

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“…Similarly, PRL levels increased in response to mu agonists in rats (Koenig et al, 1984;Limonta et al, 1987;Matton et al, 1991;Pan and Teo, 1989;Shin et al, 1988;Simpkins et al, 1991;Spiegel et al, 1982), sheep (Parrott and Goode, 1993), and rhesus monkeys (Bowen et al, 2002;Gilbeau et al, 1985).…”

Section: Preclinical Studies Of Prolactin Interactions With Kappa Andmentioning

confidence: 92%

“…Mu opioid agonists also stimulate PRL release under some conditions (Bowen et al, 2002;Hoehe et al, 1988;Saarialho-Kere et al, 1989), but inhibit ACTH and cortisol (Auernhammer et al, 1992(Auernhammer et al, , 1994. In contrast, selective mu-antagonists such as beta-FNA decrease PRL in rats (Baumann and Rabii, 1991;Koenig et al, 1984) and block morphine-induced ACTH release in rats (Pfeiffer et al, 1985). In rhesus monkeys, the mu antagonist quadazocine did not alter PRL levels significantly but antagonized the heroin-induced increase in PRL (Bowen et al, 2002).…”

Section: Introductionmentioning

confidence: 98%

Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers

Goletiani

Mendelson

Sholar

et al. 2007

Pharmacology Biochemistry and Behavior

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Nalbuphine (Nubain®) is a mixed action mu-kappa agonist used clinically for the management of pain. Nalbuphine and other mu-kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (P=.04) and reached peak levels of 22.1 ± 7.1 ng/ml and 54.1 ± 11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of "Sick," "Bad" and "Dizzy" were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (P=.05−.0001), and were significantly correlated with increases in PRL (P=.05−.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu-and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol.

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Differential role of the opioid μ and δ receptors in the activation of prolactin (PRL) and growth hormone (GH) secretion by morphine in the male rat

Cited by 60 publications

References 27 publications

Mu‐Selective Opioid Peptides Stimulate Prolactin Release in Lactating Rats

Mu‐Selective Opioid Peptides Stimulate Prolactin Release in Lactating Rats

Pituitary Gland: Neuropeptides, Neurotransmitters and Growth Factors

Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers

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