STUDIES ON THE LOSS OF ACETYLCHOLINE SENSITIVITY IN ILEAL MUSCLE

¹ Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana

The magnitude of the acetylcholine (ACh)-induced contractile response of isolated strips of guinea-pig ileal longitudinal smooth muscle gradually declines during long-term exposure to the cholinergic agent. Nonspecific desensitization also develops. Sodium ions (Na⁺) are gained by the tissue during the initial minutes of exposure but are later extruded. The decline in the ACh response is less in the presence of ouabain while Na⁺ gain and retention are enhanced. Loss of sensitivity and gain of Na⁺ is absent in low Na⁺ solution. When muscles previously in contact with Ca⁺⁺-rich solution for 2 hours are transferred to a Ca⁺⁺-free environment, they undergo a substantial contraction lasting 30 to 60 minutes and gain Na⁺. However, they do not appear to lose sensitivity to the stimulus afforded by the Ca⁺⁺-free medium. If ACh is present in the Ca⁺⁺-free medium, loss of sensitivity to stimulation provided by both ACh and the Ca⁺⁺-free enviroument is observed except when the bathing medium is low in Na⁺. The data suggest that the loss of sensitivity during exposure to ACh involves not only accumulation but also extrusion of Na⁺ by the muscle strips. The results have been interpreted to suggest that the cholinergic agent induces a redistribution of Na⁺ so as to interfere with the processes linking stimulation and contraction.