Histamine‐induced Progression From Heterologous to Homologous Desensitization of Contraction in Smooth Muscle of Guinea‐pig Taenia Caeci

Abstract

1. We have reported previously that, in the smooth muscle of guinea-pig taenia caeci, the development of carbachol-induced desensitization to carbachol and histamine has a similar time-course whereas desensitization to high K(+) is interrupted by sustained resensitization. 2. In the present study, we evaluated the development of histamine-induced desensitization to histamine, carbachol and high K(+) with respect to their regulation by resensitization, and compared it with carbachol-induced desensitization. 3. Desensitization to histamine developed following pretreatment with 10(-5) mol/L histamine for 30 min with a tendency of transient interruption by resensitization at 1 min. In contrast, histamine-induced desensitization to carbachol and high K(+) was transient, peaking at around 15 s and 2 min, respectively, followed by sustained resensitization up to complete restoration within 2 and 10 min, respectively. 4. Thus, in contrast with carbachol, histamine initially induces heterologous desensitization, followed by sustained resensitization to carbachol and high K(+), resulting in selective and sustained homologous desensitization to histamine. 5. Thus, differences in the development of histamine- and carbachol-induced heterologous desensitization/resensitization contribute to the selective regulation of receptor-mediated signal transduction pathways.

Desensitization of depolarization‐mediated contractile pathways does not necessarily regulate receptor‐mediated excitation–contraction coupling in longitudinal smooth muscle of guinea pig ileum

“…In the presence of extracellular Ca, carbachol‐induced desensitization to carbachol developed with interruption by an obscure phase of transient resensitization in its early stage in this smooth muscle. Such a peculiar phenomenon was also observed in agonist‐induced desensitization in smooth muscle of guinea pig taenia caeci 14,22–26 . as well as in human astrocytoma cells, 27 where calmodulin‐dependent protein kinase II and protein phosphatase 2B are thought to be involved in the early phase of desensitization and resensitization, respectively 27 .…”

“…Such a peculiar phenomenon was also observed in agonist-induced desensitization in smooth muscle of guinea pig taenia caeci. 14,[22][23][24][25][26] as well as in human astrocytoma cells, 27 where calmodulin-dependent protein kinase II and protein phosphatase 2B are thought to be involved in the early phase of desensitization and resensitization, respectively. 27 It is possible that transient resensitization mechanisms are conserved widely among cells or tissues and play a significant role in modulating the initial process of desensitization for further regulation of cellular homeostasis.…”

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

“…This is consistent with our previousˆndings on Ca 2＋ -dependent development of carbachol-induced heterologous desensitization in this smooth muscle. 8) In astrocytoma cells, we have found that Ca 2＋ /calmodulin-mediated processes are involved in the initial process of histamine-induced desensitization to histamine. 14 15) It is possible that such Ca 2＋ -dependent mechanisms are involved in the initial development of histamineinduced heterologous desensitization under normal physiological conditions.…”

“…Strips of taenia caeci were prepared from guinea pigs, weighing 250 400 g, as described previously. 8) The muscle strips were maintained in normal Locke-Ringer solution (normal solution), pH 7.8 at 30°C, with the following composition (mM): NaCl 154, KCl 5.6, CaCl 2 2.2, MgCl 2 2.1, NaHCO 3 6 and glucose 5.6. Contractions were induced cumulatively with histamine (10 -8 to 10 -4 M), carbachol (10 -9 to 10 -4 M) or isotonic K ＋ -rich solution (high K ＋ solution; 10 to 42 mM of K ＋ ) at 30°C.…”