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NEUROPHARMACOLOGY

Influence of Ovarian Sex Steroids on Spinal Methionine-Enkephalin Release: Comparison with Dynorphin Reveals Asymmetrical Regulation

Department of Biochemistry, State University of New York, Downstate Medical Center, Brooklyn, New York

The concomitant activation of spinal -and -opioid systems is a prerequisite for the antinociception of gestation and its hormonal simulation [via 17-estradiol and progesterone administration; hormone-simulated pregnancy (HSP)]. However, it is not known whether the release of -and -opioids is also concomitantly regulated. This study investigates whether the release of methionine-enkephalin and modulation thereof is altered during HSP, as has been reported for dynorphin. K⁺-stimulated release of spinal methionine-enkephalin from lumbar spinal tissue obtained from control animals is negatively modulated by nociceptin (orphanin FQ; N/OFQ) in a dose-dependent manner, but not by opioids. Conversely, selective blockade of spinal N/OFQ, but not opioid receptors, augments the K⁺-induced increase in methionine-enkephalin release, indicating that endogenous N/OFQ also functions as a negative modulator of methionine-enkephalin release. The magnitude of K⁺-evoked methionine-enkephalin release from spinal tissue obtained from ovarian steroid-treated animals remains unchanged, consistent with the insensitivity of its modulation by N/OFQ to the ovarian sex steroid milieu. These characteristics of methionine-enkephalin release stand in sharp contrast to those previously reported for the evoked release of spinal dynorphin. Dynorphin release is subject to negative modulation by opioid (predominantly ) as well as N/OFQ, both of which are offset during HSP, resulting in an 2-fold increase in the magnitude of its release. These observations reveal that regulation of spinal dynorphin/-and methionine-enkephalin/-spinal opioid antinociceptive systems is independent, divergent, and not symmetrical and support the formulation that spinal methionine-enkephalin/-opioid tone acts in a permissive/facilitative capacity to accentuate spinal dynorphin/-activity.

Address correspondence to: Dr. Alan Gintzler, Department of Biochemistry, Box 8, SUNY Downstate Medical Center, 450 Clarkson Ave., Brooklyn, NY 11203. E-mail: agintzler{at}netmail.hscbklyn.edu

This article has been cited by other articles:

				D. S. Gupta, H. von Gizycki, and A. R. Gintzler Sex-/Ovarian Steroid-Dependent Release of Endomorphin 2 from Spinal Cord J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 635 - 641. [Abstract] [Full Text] [PDF]

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