Histamine H3 receptor desensitization in the guinea-pig ileum

Histamine H-3 receptor ligands are usually tested in guinea-pig intestine preparations. A possible desensitization of agonist-induced twitch inhibition was studied in longitudinal muscle-myenteric plexus from ileal segments. A cumulative concentration-response curve for R-alpha-methylhistamine was made; when a second curve was made 30 min afterwards, a marked decrease of pD(2), and a more modest decrease of E-max were observed without changes in tissue sensitivity to electrical stimulation or morphine inhibition. At 120 min, pD(2) and E-max were not different from those for the first curve. Receptor desensitization seems homologous and reversible and could interfere max with repetitive testing of histamine H-3 receptor ligands. (C) 1998 Elsevier Science B.V.