• A B Lohmann and S P Welch.
• Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Box 980613, Richmond, VA 23298-0613, USA.
• Eur. J. Pharmacol. 1999 Nov 19; 384 (2-3): 147-52.

AbstractThe ATP-gated K(+) channel openers diazoxide, levcromakalim and morphine induce cell hyperpolarization by opening the K(+) channels and enhancing K(+) efflux. This hyperpolarization decreases intracellular Ca(2+) levels, lessening neurotransmitter release thus leading to antinociception. Previous findings implicate the release of endogenous opioids as the mediator of the antinociceptive effects of ATP-gated K(+) channel openers. Antisense oligodeoxynucleotides to the opioid receptor clones, which decrease the number of available receptors, were used to demonstrate the involvement of endogenous opioids in diazoxide- and levcromakalim-induced antinociception. Antisense to all three opioid receptors attenuated the effect of diazoxide, suggesting that diazoxide is inducing the release of endogenous opioids activating the mu(MOR-1)-, delta(DOR-1)-, and kappa(KOR-1)-opioid receptors. Antisense to the mu-opioid receptor clone and delta-opioid receptor clone attenuated levcromakalim-induced antinociception, indicating that endogenous opioids acting at the mu- and delta-opioid receptors are potential candidates for the mediation of the antinociceptive effects of levcromakalim.

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