HISTAMINE H-1 RECEPTORS AND INOSITOL PHOSPHATE FORMATION IN RAT THALAMUS

In membranes of rat thalamus the density of histamine Hi receptors, as estimated from saturation curves with [H-3]mepyramine, was 66 +/- 5 f mol.mg protein(-1) (K-d 1.3 +/- 0.1 nM). Specific [H-3]mepyramine bind ing was inhibited by mepyramine (best fit to one-site model, K-d 2.2 /- 0.2 nM) and by histamine (best fit to a two-site model, K-i high 0. 35 +/- 0.04 mu M and 54 +/- 7% of binding sites; K-i low 7.0 +/- 1.1 m u M). In the presence of 300 mu M GppNHp (5'-guanylylimidodiphosphate) the inhibition curve for histamine best-fit to a one-site model (K-i 3.1 +/- 0.3 mu M) In cross-chopped slices and in the presence of 10 mM LiCl, histamine stimulated the accumulation of total [H-3]inositol ph osphates ([H-3]LPs) with a maximum effect of 163 +/- 3% of basal accum ulation, EC50 of 8 +/- 2 mu M and Hill coefficient (n(H)) of 0.8 +/- 0 .1. [H-3]IPs accumulation induced by 100 mu M histamine was inhibited by the selective H-1 antagonist mepyramine (1 mu M, 90 +/- 8% inhibiti on; K-i 2.1 +/- 0.4 nM) but not by 10 mu M ranitidine (a selective H-2 antagonist) or 1 mu M thioperamide (a selective H-3 antagonist). Thes e results show the presence in rat thalamus of functional Hi receptors coupled to inositol phosphate accumulation. (C) 1997 Elsevier Science Ireland Ltd.