Journal of biomedical science
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The midbrain periaqueductal gray matter (PAG) is an important brain region for the coordination of mu-opioid-induced pharmacological actions. The present study was designed to determine whether newly isolated mu-opioid peptide endomorphins can activate G proteins through mu-opioid receptors in the PAG by monitoring the binding to membranes of the non-hydrolyzable analog of GTP, guanosine-5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS). An autoradiographic [(35)S]GTPgammaS binding study showed that both endomorphin-1 and -2 produced similar anatomical distributions of activated G proteins in the mouse midbrain region. ⋯ Coincubation with selective mu-opioid receptor antagonists beta-funaltrexamine or D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Phe-Thr-NH(2) (CTOP) blocked both endomorphin-1 and-2-stimulated [(35)S]GTPgammaS binding. In contrast, neither delta- nor kappa-opioid receptor antagonist had any effect on the [(35)S]GTPgammaS binding stimulated by either endomorphin-1 or -2. These findings indicate that both endomorphin-1 and -2 increase [(35)S]GTPgammaS binding by selectively stimulating mu-opioid receptors with intrinsic activity less than that of DAMGO and suggest that these new endogenous ligands might be partial agonists for mu-opioid receptors in the mouse PAG.
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We examined scratch-inducing effects of intracisternal, intrathecal and intradermal injections of morphine and some opioid agonists in mice. Intracisternal injection of morphine (3 nmol/animal) and the mu-receptor agonist [D-Ala(2), N-Me-Phe(4), Gly(5)-ol]enkephalin (DAMGO; 0.2 nmol/animal) elicited scratching of the face, with little effect on scratching of the trunk. Intracisternal injection of the delta-receptor agonist [D-Pen(2,5)]enkephalin (DPDPE) and the kappa-receptor agonist U50488 were without effects. ⋯ Intradermal injections of morphine (3-100 nmol/site), DAMGO (1-100 nmol/site), DPDPE (10 and 100 nmol/site) and U50488 (10-100 nmol/site) did not elicit scratching of the site of injection. Intradermal injection of histamine (100 nmol/site) induced the scratching in ICR, but not ddY, mice and serotonin (30 and 50 nmol/site) elicited the scratching in either strain of mice. The results suggest that opioids induce scratching, and probably itching, through central mu-opioid receptors in the mouse.