ISSN:
1432-2013
Keywords:
Key words G proteins
;
NG108
;
15 cells
;
N-type Ca2+ channels
;
Opioids
;
δ-Opioid receptors
;
Whole-cell patch clamp
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Opioids have both inhibitory and stimulatory effects on neurotransmitter release. While the inhibitory effect has been ascribed to presynaptic inhibition of Ca2+ channels, the cellular mechanism underlying the stimulatory effect is not clear. In order to address this issue, we analyzed the effects of [d-Ala2, d-Leu5]-enkephalin (DADLE) on whole-cell Ba2+ currents (I Ba) through voltage-gated Ca2+ channels in NG108–15 neuroblastoma × glioma hybrid cells. Application of DADLE inhibited and washout of DADLE transiently potentiated I Ba. Furthermore, potentiation of I Ba was elicited even in the presence of DADLE, when inhibition was relieved by a large depolarizing prepulse. DADLE-induced potentiation, as well as inhibition, had both voltage-sensitive and -insensitive components and was abolished by treatment with ICI174864, a δ-opioid antagonist, pertussis toxin (PTX) and ω-conotoxin GVIA. Potentiation developed over @3 min and took 5–20 min to recover, whereas inhibition was complete within 30 s and recovered within 1 min. Although this potentiation should contribute to DADLE-induced desensitization of Ca2+ channel inhibition, it was not the sole mechanism for desensitization. We conclude that the δ-opioid receptor exerts a dual action on N-type Ca2+ channels via PTX-sensitive G proteins, i.e., rapid inhibition followed by slowly developing potentiation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00008091
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