Histamine H₁ receptors and inositol phosphate formation in rat thalamus

In membranes of rat thalamus the density of histamine H₁ receptors, as estimated from saturation curves with [³H]mepyramine, was 66 ± 5 fmol.mg protein^-1 (K(d) 1.3 ± 0.1 nM). Specific [³H]mepyramine binding 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(± high) 0.35 ± 0.04 μM and 54 ± 7% of binding sites; K(± low) 7.0 ± 1.1 μM). In the presence of 300 μM GppNHp (5'-guanylylimidodiphosphate) the inhibition curve for histamine best-fit to a one-site model (K(i) 3.1 ± 0.3 μM). In cross-chopped slices and in the presence of 10 mM LiCl, histamine stimulated the accumulation of total [³H]inositol phosphates ([³H]IPs) with a maximum effect of 163 ± 3% of basal accumulation, ECS₅₀ of 8 ± 2 μM and Hill coefficient (n(H)) of 0.8 ± 0.1. [³H]IPs accumulation induced by 100 μM histamine was inhibited by the selective H₁ antagonist mepyramine (1 μM, 90 ± 8% inhibition; K(i) 2.1 ± 0.4 nM) but not by 10 μM ranitidine (a selective H₂ antagonist) or 1 μM thioperamide (a selective H₃ antagonist). These results show the presence in rat thalamus of functional H₁ receptors coupled to inositol phosphate accumulation.