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Desensitization and resensitization of delta-opioid receptor-mediated Ca2+ channel inhibition in NG108-15 cells.
Br J Pharmacol. 1998 Mar; 123(6):1111-8.BJ

Abstract

1. To approach the mechanisms underlying desensitization of the opioid receptor-mediated Ca2+ channel inhibition, the effects of prolonged application of [D-Ala2, D-Leu5]enkephalin (DADLE) on Ba2+ currents (I(Ba)) through Ca2+ channels were analysed in NG108-15 neuroblastoma x glioma hybrid cells. 2. Inhibition of I(Ba) by 100 nM DADLE desensitized by 57% with a time constant of 4.4 min. 3. Maximal desensitization of the delta-opioid receptor-Ca2+ channel coupling was attained by 1 microM DADLE. The EC50 value for desensitization was estimated to be 78 nM. 4. RNA blot hybridization analysis and immunoblot analysis revealed the expression of beta-adrenoceptor kinase-1 (betaARK1) in NG108-15 cells. 5. Heparin, an inhibitor of betaARK, significantly reduced the magnitude and rate of desensitization, whereas Rp-cyclic AMPS and PKI (14-24)amide, inhibitors of cyclic AMP-dependent protein kinase (PKA), or long-term treatment with phorbol 12-myristate 13-acetate to induce down-regulation of protein kinase C (PKC) had no significant effect. 6. Recovery from desensitization (resensitization) proceeded with a time constant of 6.7 min. Okadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, significantly attenuated the degree of resensitization. 7. In summary, we have characterized the time course and concentration-dependence of the desensitization of DADLE-induced I(Ba) inhibition in NG108-15 cells. This desensitization was reversible after removal of DADLE. It is suggested that betaARK, but neither PKA nor PKC, is involved in desensitization, while serine/threonine phosphatases mediate resensitization.

Authors+Show Affiliations

Department of Anesthesia, Kyoto University Hospital, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9559894

Citation

Morikawa, H, et al. "Desensitization and Resensitization of Delta-opioid Receptor-mediated Ca2+ Channel Inhibition in NG108-15 Cells." British Journal of Pharmacology, vol. 123, no. 6, 1998, pp. 1111-8.
Morikawa H, Fukuda K, Mima H, et al. Desensitization and resensitization of delta-opioid receptor-mediated Ca2+ channel inhibition in NG108-15 cells. Br J Pharmacol. 1998;123(6):1111-8.
Morikawa, H., Fukuda, K., Mima, H., Shoda, T., Kato, S., & Mori, K. (1998). Desensitization and resensitization of delta-opioid receptor-mediated Ca2+ channel inhibition in NG108-15 cells. British Journal of Pharmacology, 123(6), 1111-8.
Morikawa H, et al. Desensitization and Resensitization of Delta-opioid Receptor-mediated Ca2+ Channel Inhibition in NG108-15 Cells. Br J Pharmacol. 1998;123(6):1111-8. PubMed PMID: 9559894.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Desensitization and resensitization of delta-opioid receptor-mediated Ca2+ channel inhibition in NG108-15 cells. AU - Morikawa,H, AU - Fukuda,K, AU - Mima,H, AU - Shoda,T, AU - Kato,S, AU - Mori,K, PY - 1998/4/29/pubmed PY - 1998/4/29/medline PY - 1998/4/29/entrez SP - 1111 EP - 8 JF - British journal of pharmacology JO - Br J Pharmacol VL - 123 IS - 6 N2 - 1. To approach the mechanisms underlying desensitization of the opioid receptor-mediated Ca2+ channel inhibition, the effects of prolonged application of [D-Ala2, D-Leu5]enkephalin (DADLE) on Ba2+ currents (I(Ba)) through Ca2+ channels were analysed in NG108-15 neuroblastoma x glioma hybrid cells. 2. Inhibition of I(Ba) by 100 nM DADLE desensitized by 57% with a time constant of 4.4 min. 3. Maximal desensitization of the delta-opioid receptor-Ca2+ channel coupling was attained by 1 microM DADLE. The EC50 value for desensitization was estimated to be 78 nM. 4. RNA blot hybridization analysis and immunoblot analysis revealed the expression of beta-adrenoceptor kinase-1 (betaARK1) in NG108-15 cells. 5. Heparin, an inhibitor of betaARK, significantly reduced the magnitude and rate of desensitization, whereas Rp-cyclic AMPS and PKI (14-24)amide, inhibitors of cyclic AMP-dependent protein kinase (PKA), or long-term treatment with phorbol 12-myristate 13-acetate to induce down-regulation of protein kinase C (PKC) had no significant effect. 6. Recovery from desensitization (resensitization) proceeded with a time constant of 6.7 min. Okadaic acid, an inhibitor of serine/threonine phosphatases 1 and 2A, significantly attenuated the degree of resensitization. 7. In summary, we have characterized the time course and concentration-dependence of the desensitization of DADLE-induced I(Ba) inhibition in NG108-15 cells. This desensitization was reversible after removal of DADLE. It is suggested that betaARK, but neither PKA nor PKC, is involved in desensitization, while serine/threonine phosphatases mediate resensitization. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9559894/Desensitization_and_resensitization_of_delta_opioid_receptor_mediated_Ca2+_channel_inhibition_in_NG108_15_cells_ L2 - https://doi.org/10.1038/sj.bjp.0701733 DB - PRIME DP - Unbound Medicine ER -