FUNCTIONAL-CHARACTERIZATION OF ALPHA(1)-ADRENOCEPTOR SUBTYPES MEDIATING NORADRENALINE-INDUCED INOSITOL PHOSPHATE FORMATION IN RAT THALAMUS SLICES

In cross-chopped slices from rat thalamus and in the presence of 10 mM LiCl, noradrenaline stimulated the accumulation of [H-3]inositol phos phates with [H-3]inositol monophosphates ([H-3]IP1) being the major pr oduct detected (86 +/- 2% of total [H-3]inositol phosphates). Noradren aline-induced [H-3]IP1 accumulation was concentration-dependent and yi elded an EC(50) of 4.6 +/- 0.2 mu M, maximum effect of 272 +/- 3% of b asal formation and Hill coefficient (n(H)) of 1.6 +/- 0.1. The effect of 100 mu M noradrenaline was inhibited by the alpha(1)-adrenoceptor a ntagonists prazosin, (+)-niguldipine, 5-methylurapidil and WE-4101 (2- (2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane). The inhibit ion curve for prazosin best fit to a single-site model whereas curves for (+)-niguldipine, 5-methylurapidil and WE-4101 best fit to a two-si te model. The putative alpha(1D)-adrenoceptor-selective antagonist BMY 7378 iperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione) showed low po tency and efficacy to inhibit the response to noradrenaline. Pre-treat ment of the slices with chloroethylclonidine (100 mu M; 30 min) decrea sed by 64 +/- 4% the maximum response. Noradrenaline-induced [H-3]IP1 accumulation was significantly reduced by Ca2+ removal (by 64 +/- 2%) and by the Ca2+-channel blockers Ni2+, Co2+ and nimodipine (inhibition of 56 +/- 6%, 54 +/- 5% and 41 +/- 5%, respectively). Taken together these results indicate that noradrenaline-induced inositol phosphate f ormation in thalamus slices is mainly mediated by the activation of bo th alpha(1B), and alpha(1A) subtypes of alpha(1)-adrenoceptors.