HISTAMINE-INDUCED PROGRESSION FROM HETEROLOGOUS TO HOMOLOGOUS DESENSITIZATION OF CONTRACTION IN SMOOTH MUSCLE OF GUINEA-PIG TAENIA CAECI

SUMMARY 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.