Homologous histamine H1 receptor desensitization results in reduction of H1 receptor agonist efficacy.
Prolonged exposure of the guinea-pig intestinal longitudinal smooth muscle to histamine caused homologous desensitization of the H1 receptor, which led to reduced H1 receptor-mediated production of [3H]inositol phosphates as well as to reduced H1 agonist-induced contractions. [3H]Mepyramine binding studies showed that desensitization affected neither the agonist affinity nor the number of H1 receptors. Combining the data from the binding studies and the contraction measurements it was found that desensitization results in a selective reduction of agonist efficacy.
Leurs
R
R
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, The Netherlands.
Smit
M J
MJ
Bast
A
A
Timmerman
H
H
D000818:Animals; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008566:Membranes / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D011738:Pyrilamine / Q000378:metabolism / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014316:Tritium
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011725:Pyridines; D011969:Receptors, Histamine H1; D014316:Tritium; D006632:Histamine; C006183:2-(2-aminoethyl)pyridine; D011738:Pyrilamine