Article date: June 1997
By: Shuji Kaneko, Nobumichi Yada, Koichiro Fukuda, Masanobu Kikuwaka, Akinori Akaike, Masamichi Satoh, in Volume 121, Issue 4, pages 806-812
Desensitization of μ‐ and κ‐opioid receptor‐mediated inhibition of voltage‐dependent Ca2+ channels was studied in a Xenopus oocyte translation system.
In the oocytes coexpressing κ‐opioid receptors with N‐ or Q‐type Ca2+ channel α1 and β subunits, the κ‐agonist, U50488H, inhibited both neuronal Ca2+ channel current responses in a pertussis toxin‐sensitive manner and the inhibition was reduced by prolonged agonist exposure.
More than 10 min was required to halve the inhibition of Q‐type channels by the κ‐agonist. However, the half‐life for the inhibition of N‐type channels was only 6±1 min. In addition, in the oocytes coexpressing μ‐opioid receptors with N‐type or Q‐type channels, the uncoupling rate of the μ‐receptor‐mediated inhibition of N‐channels was also faster than that of Q‐type channels.
In the oocytes coexpressing both μ‐ and κ‐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 μM), staurosporine (400 nM), okadaic acid (200 nM), phorbol myristate acetate (5 nM) or forskolin (50 μM) plus phosphodiesterase inhibitor did not affect either the desensitization or the agonist‐evoked inhibition of Ca2+ channels.
These results suggest that the rate of rapid desensitization is dependent on the α1 subtype of the neuronal Ca2+ channel, and that a common phosphorylation‐independent mechanism underlies the heterologous desensitization between opioid receptor subtypes.
Desensitization of μ‐ and κ‐opioid receptor‐mediated inhibition of voltage‐dependent Ca2+ channels was studied in a Xenopus oocyte translation system.
In the oocytes coexpressing κ‐opioid receptors with N‐ or Q‐type Ca2+ channel α1 and β subunits, the κ‐agonist, U50488H, inhibited both neuronal Ca2+ channel current responses in a pertussis toxin‐sensitive manner and the inhibition was reduced by prolonged agonist exposure.
More than 10 min was required to halve the inhibition of Q‐type channels by the κ‐agonist. However, the half‐life for the inhibition of N‐type channels was only 6±1 min. In addition, in the oocytes coexpressing μ‐opioid receptors with N‐type or Q‐type channels, the uncoupling rate of the μ‐receptor‐mediated inhibition of N‐channels was also faster than that of Q‐type channels.
In the oocytes coexpressing both μ‐ and κ‐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 μM), staurosporine (400 nM), okadaic acid (200 nM), phorbol myristate acetate (5 nM) or forskolin (50 μM) plus phosphodiesterase inhibitor did not affect either the desensitization or the agonist‐evoked inhibition of Ca2+ channels.
These results suggest that the rate of rapid desensitization is dependent on the α1 subtype of the neuronal Ca2+ channel, and that a common phosphorylation‐independent mechanism underlies the heterologous desensitization between opioid receptor subtypes.
British Journal of Pharmacology (1997) 121, 806–812; doi:10.1038/sj.bjp.0701181
DOI: 10.1038/sj.bjp.0701181
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