Histamine Develops Homologous Desensitization under Ca²⁺-free Conditions with Increase in Basal Tone in Smooth Muscle of Guinea Pig Taenia Caeci

抄録

  Histamine regulates a variety of physiological or pathophysiological processes via the activation of G_q/11 protein-coupled and Ca²⁺-mobilizing histamine H₁ receptors, including smooth muscle contraction. We have found that histamine induces progression from heterologous to homologous desensitization of contraction under normal physiological conditions in smooth muscle of guinea pig taenia caeci. In this study, we characterized the development of histamine-induced desensitization under Ca²⁺-free conditions and we found that histamine developed only a homologous phase of desensitization to histamine with an increase in EC₅₀ values for histamine and basal tone. In contrast, histamine treatment reduced EC₅₀ values for a muscarinic agonist, carbachol, and depolarizing high K⁺. These results suggest that the failure of excess histamine to induce a normal Ca²⁺ response under Ca²⁺-free conditions may lead to homologous desensitization to histamine with apparent hyper-reactivity of smooth muscles to cholinergic and depolarizing stimuli. We estimate that this characteristic of histamine to change smooth muscle contractility may be potentially involved in its physiological and pathophysiological aspects, including histamine-induced allergic conditions, depending on cellular circumstances.