INHIBITION OF MUSCARINIC RECEPTOR-OPERATED CA2-TERM DESENSITIZATION OF ALPHA-TOXIN-PERMEABILIZED SMOOTH-MUSCLE CELLS FROM GUINEA-PIG STOMACH( SENSITIZATION BY SHORT)

1. Isolated single smooth muscle cells from the guinea pig stomach wer e permeabilized with Staphylococcus aureus alpha-toxin. 2. The permeab ilized single cells showed a shortening in response to Ca2+ in an all- or-none manner. Moreover, the addition of acetylcholine (ACh) or guano sine 5'-triphosphate (GTP) resulted in a decrease in concentration of Ca2+ required to trigger a threshold response, suggesting that Ca2+ se nsitization is induced by the stimulation of muscarinic acetylcholine receptors (mAChRs) or GTP-binding protein(s). 3. Short-term desensitiz ation was induced by incubating the permeabilized cells with 100 mu M ACh for 10 min. 4. In desensitized cells, the concentration of Ca2+ re quired to trigger a threshold response in the presence of ACh was incr eased, however, the cell shortening in response to Ca2+ in the absence of ACh and GTP induced Ca2+ sensitization was not affected by short-t erm desensitization. 5. These results suggest that the receptor operat ed augmentation of Ca2+ sensitivity is inhibited by short-term desensi tization and that the development of short-term desensitization is due to an uncoupling of mAChR/GTP-binding protein(s). (C) 1997 Elsevier S cience Inc.