Abstract

Specific desensitization or taehyphylaxis has not been demonstrated convincingly in smooth muscle with nonpolypeptide directly acting agonists. Guinea-pig ileum is said to show only nonspecific desensitization to various drugs and other stimuli (Herrlinger J.-D., Lullmann, H. and Schuh, F.: Naunyn-Schnmiedebergs Arch. Pharnmakol. 256: 348-355, 1967). On the premise that nonspecific desensitizatioim usually masks tachyphylaxis, isolated ileum was deprived of calcium and then exposed to high concentrations (4 x 10^-4 M) of histamine or furtrethonium in Ca⁺⁺-free solutions to avoid contractions. Drug exposure periods of two and six minutes were tested. After drug washout and calcium restoration, desensitization to low concentrations of both drugs was denmonstrable in terms of impaired isotonic contractile responses. Recovery to furtrethonium, however, was faster than recovery to histamine after desensitization by histamine, whereas the opposite was usually true after desensitization by furtrethonium. This pattern occurred after drug exposure periods of six but not of two minutes. Thus, both specific and nonspecific processes contributed to the total desensitization induced by time longer exposure, whereas only nonspecific desensitization was evident after the shorter exposure. A possible mechanism of tachphylaxis is suggested.