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 (Kd 1.3 +/- 0.1 nM). Specific [3H]mepyramine binding was inhibited by mepyramine (best fit to one-site model, Kd 2.2 +/- 0.2 nM) and by histamine (best fit to a two-site model, Ki high 0.35 +/- 0.04 microM and 54 +/- 7% of binding sites; Ki low 7.0 +/- 1.1 microM). In the presence of 300 microM GppNHp (5'-guanylylimidodiphosphate) the inhibition curve for histamine best-fit to a one-site model (Ki 3.1 +/- 0.3 microM). 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, EC50 of 8 +/- 2 microM and Hill coefficient (nH) of 0.8 +/- 0.1. [3H]IPs accumulation induced by 100 microM histamine was inhibited by the selective H1 antagonist mepyramine (1 microM, 90 +/- 8% inhibition; Ki 2.1 +/- 0.4 nM) but not by 10 microM ranitidine (a selective H2 antagonist) or 1 microM thioperamide (a selective H3 antagonist). These results show the presence in rat thalamus of functional H1 receptors coupled in inositol phosphate accumulation.
Soria-Jasso
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LE
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, México, D.F., México.
Bahena-Trujillo
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R
Arias-Montaño
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JA
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000096:biosynthesis*; D011738:Pyrilamine / Q000494:pharmacology*; D051381:Rats; D011969:Receptors, Histamine H1 / Q000187:drug effects*; D013788:Thalamus / Q000187:drug effects*
D007295:Inositol Phosphates; D011969:Receptors, Histamine H1; D006632:Histamine; D011738:Pyrilamine