Histamine-induced progression from heterologous to homologous desensitization of contraction in smooth muscle of guinea-pig taenia caeci.
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.
Hishinuma
Shigeru
S
Department of Pharmacodynamics, Meiji Pharmaceutical University, Tokyo, Japan. hishi@my-pharm.ac.jp
Saito
Masaki
M
D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D006632:Histamine