Opioids acting through delta receptors elicit a transient increase in the intracellular free calcium concentration in dorsal root ganglion-neuroblastoma hybrid ND8-47 cells
Tang, T.; Kiang, J.G.; Cox, B.M.
Journal of Pharmacology and Experimental Therapeutics 270(1): 40-46
1994
ISSN/ISBN: 0022-3565 PMID: 8035339 Document Number: 428922
The neuronal cell line ND8-47 (neuroblastoma times dorsal root ganglion neuron hybrid) expressed opioid delta-type receptors. We report opioid-induced changes in cytosolic intracellular free calcium ((Ca++)-i) in differentiated ND8-47 cells. Delta-opioid receptor agonists induced a transient ( lt 2 min) increase in (Ca++)-i in a concentration-dependent fashion with the potency order: (D-Ser-2,Leu-5)enkephalin-Thr (DSLET) gtoreq deltorphin II gt (D-Pen-2,5) enkephalin. Their effects were blocked by naloxone (IC-50 = 20 nM) and naltrindole (IC-50 = 2.5 nM). Selective mu and kappa receptor agonists had no effect on (Ca++)-i. The subtype specific delta receptor antagonists, 7-benzylidene naltrexone (delta-1) and naltriben (delta-2), were used to characterize further the subtype of delta receptors mediated by this response. Naltriben was more potent than 7-benzylidene naltrexone in antagonizing the DSLET-induced increase in (Ca++)-i. The increase in (Ca++)-i induced by DSLET was blocked by nifedipine (1 mu-M) or verapamil (1 mu-M), and was not observed in the absence of external calcium. Changes in (Ca++)-i also were measured in single ND8-47 cells. The percentage of cells responding to DSLET (1 mu-M), deltorphin-II (1 mu-M) and (D-Pen-2,5)enkephalin (1 mu-M) were 86, 84 and 37%, respectively. The results suggest that an increase in (Ca++)-i induced by opioids is mediated through opioid delta receptors which can activate dihydropyridine-sensitive Ca++ channels.