Opioid κ Receptors and the Secretion of Prolactin (PRL) and Growth Hormone (GH) in the Rat

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Abstract
An analysis of the GH release-inhibiting action of the opioid Kreceptor agonists bremazocine and U-50,488, established earlier, was attempted by testing the agonists against activation of GH secretion by morphine or clonidine in male rats bearing right atrial cannulae for serial blood sampling and drug delivery. Both ĸ agonists inhibited the effect of subsequent administration of clonidine in a dose-related manner. Bremazocine was approximately ten times more potent than U-50,488, a ratio corresponding to the known affinities of the two compounds for the ĸ receptors. The inhibiting action of bremazocine was more strongly reversed by the preferential ĸ receptor antagonist Mr-2266 than by naloxone, neither of which interfered with the GH-stimulating effect of clonidine. Bremazocine, however, did not alter the activation of GH secretion by exogenous growth hormone releasing factor. Thus, the inhibiting effect of bremazocine and probably U-50,488 seems to be derived from stimulation of the ĸ receptors which in turn activates a GH release inhibiting mechanism of unknown identity which, however, does not involve release of somatostatin. Both Kagonists also inhibited the effect of morphine, but in this case U-50,488 was approximately hundred times less effective than bremazocine. Since bremazocine and U-50,488 are antagonists of the ĸ receptors, which seem to mediate the GH-releasing effect to morphine, their inhibiting effect in this instance may be related to this property rather than to an action on the ĸ receptors. Bremazocine, but not U-50,488, was also highly effective in inhibiting stimulation of PRL secretion by morphine. Stimulation of PRL by morphine is mediated by the µi type of opioid receptors, and the inhibiting effect of bremazocine may reflect its antagonist action on these receptors not shared by U-50,488. In conclusion, our data indicate that the ĸ receptors may participate in the regulation of GH secretion conveying an inhibitory influence. They also demonstrate the complexity of actions of the Kreceptor agonists derived from their multiple and varied interactions with the different receptor types.