Carbachol-induced nonspecific desensitization in guinea-pig ileum

The effects of repeated stimulation by carbachol on force development have been examined in smooth muscle of the longitudinal layer of the guinea-pig ileum. Carbachol was applied at 20 degrees C for 5 min. Each application was followed by a 25-min washout period and the desensitization was expressed by the decline of the maximal force development. Three hours after the first carbachol-induced contraction the peak amplitude was about 40% of the initial value. Increasing the frequency of application, thereby decreasing the washout time, enhanced the desensitization, while the presence of the competitive blocker atropine reduced the phenomenon. At 35 degrees C no desensitization could be observed. Blocking the Na+/K+ pump by ouabain or by K(+)-free solution reduced the force development to less than 20%. Increasing [K+]0 in the washout solution at 20 degrees C reduced the desensitization phenomenon, while decreasing [K+]0 resulted in an enhanced desensitization as expressed by a decline of the force development. The total cellular Na+ content after various stimulation sequences was determined at 20 degrees and 35 degrees C from the 22Na+ effluxes. At 35 degrees C the cellular Na+ content did not change significantly during stimulation for 10 min with 10(-4) mol/l carbachol. At 20 degrees C the resting Na+ content was significantly increased, and it doubled during carbachol stimulation for 10 min. Furthermore, the recovery of the cellular Na+ content after washout proceeded extremely slowly at that temperature. The appearance of desensitization was increased by 10 mumol/l ryanodine, while it was reduced by adding the Ca2+ agonist Bay K 8644.(ABSTRACT TRUNCATED AT 250 WORDS)