Ca2+ channel inhibition by K opioid receptors expressed in Xenopus oocytes

Abstract

1 Desensitization of m-and k-opioid receptor-mediated inhibition of voltage-dependent Ca 2+ channels was studied in a Xenopus oocyte translation system. 2 In the oocytes coexpressing k-opioid receptors with Nor Q-type Ca 2+ channel a 1 and b subunits, the k-agonist, U50488H, inhibited both neuronal Ca 2+ channel current responses in a pertussis toxin-sensitive manner and the inhibition was reduced by prolonged agonist exposure. 3 More than 10 min was required to halve the inhibition of Q-type channels by the k-agonist. However, the half-life for the inhibition of N-type channels was only 6+1 min. In addition, in the oocytes coexpressing m-opioid receptors with N-type or Q-type channels, the uncoupling rate of the m-receptor-mediated inhibition of N-channels was also faster than that of Q-type channels. 4 In the oocytes coexpressing both m-and k-receptors with N-type channels, stimulation of either receptor resulted in a cross-desensitization of the subsequent response to the other agonist. Treatment of oocytes with either H-8 (100 mM), staurosporine (400 nM), okadaic acid (200 nM), phorbol myristate acetate (5 nM) or forskolin (50 mM) plus phosphodiesterase inhibitor did not a€ect either the desensitization or the agonist-evoked inhibition of Ca 2+ channels. 5 These results suggest that the rate of rapid desensitization is dependent on the a 1 subtype of the neuronal Ca 2+ channel, and that a common phosphorylation-independent mechanism underlies the heterologous desensitization between opioid receptor subtypes.

Targeting human Mas-related G protein-coupled receptor X1 to inhibit persistent pain

“…Whereas the activation of MRGPRC leads to inhibition of HVA I Ca through a phospholipase C-dependent mechanism, our findings suggest that MRGPRX1 inhibition of HVA I Ca is mainly mediated by G i/o -sensitive Gβγ binding and may also involve a Gβγ-independent pathway. N-type channels are also an important target for opioid inhibition of pain through the G i/o pathway (39,(60)(61)(62), indicating again that MRGPRX1 may be another endogenous inhibitory mechanism parallel to the endogenous inhibitory mechanism of opioids. Importantly, MRGPRX1 is restricted to the pain pathway and may selectively modulate HVA calcium channels in primary nociceptive neurons to attenuate persistent pain.…”

Long-term spinal analgesic delivery: A review of the preclinical and clinical literature

“…This µ receptor effect is mediated by a membrane G o protein, while ␦ effects are mediated by Gi/o proteins. 63 In addition to the hyperpolarization induced by µ and ␦ agonist receptor occupancy, there is a concurrent inhibition of the opening of voltage-sensitive Ca 2ϩ channels, 64,65 which will subsequently depress the terminal release of neurotransmitters from the cell.…”

Anti-Arrhythmic Effect of Verapamil Is Accompanied by Preservation of Cx43 Protein in Rat Heart

“…Recent work from our laboratory has documented that U50,488H can prevent incidence of arrhythmias via stabilization of Cx43 protein [10]. U50,488H also elicits the effect of calcium channel blockage like verapamil [11]; however, the effect of calcium channel blockage by verapamil on Cx43 is still unclear. Therefore, the present study was designed to determine the role of Cx43 protein in verapamil-mediated antiarrhythmic effects.…”