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)
Himpens
B
B
Physiological Laboratory of the K. U. Leuven, Belgium.
Droogmans
G
G
Casteels
R
R
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D013696:Temperature; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D011453:Prostaglandins; D010566:Virulence Factors, Bordetella; D013373:Substance P; D010042:Ouabain; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001285:Atropine; D006632:Histamine; D002217:Carbachol; D012964:Sodium; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium