ISSN:
1432-1912
Keywords:
Visceral smooth muscle
;
Desensitization
;
G-proteins
;
Ca2+ agonists
;
Muscarinic stimulation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary 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°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°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°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° and 35°C from the 22Na+ effluxes. At 35°C the cellular Na+ content did not change significantly during stimulation for 10 min with 10−4 mol/l carbachol. At 20°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 μmol/l ryanodine, while it was reduced by adding the Ca2+ agonist Bay K 8644. Also the presence of pertussis toxin reduced the desensitization. The desensitizing effects of other agonists as histamine and substance P were less pronounced but also frequency dependent. The nonspecific nature of the carbachol desensitization was confirmed by the reduced response to histamine after stimulations with carbachol. We conclude that nonspecific desensitization is an agonist-, time- and temperature-dependent phenomenon. This desensitization could be the result of a G-protein-mediated inactivation of voltage-gated Ca2+ currents, which would thereby reduce the amount of [Ca2+]i mobilized during repeated stimulation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00184288
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