Ca2+-dependent differential development of carbachol-induced desensitization to receptor agonists and high K+ in guinea-pig taenia caeci.
1. Carbachol (CCh)-induced desensitization to CCh was interrupted by a transient resensitization during its early stage, with concomitant changes at the muscarinic receptor/G-protein level in smooth muscle of guinea-pig taenia caeci. To assess whether such a peculiar desensitizing process may heterologously regulate smooth muscle contraction, we examined the developmental processes of CCh-induced desensitization to histamine and high K(+) and compared it with that to CCh. 2. Under Ca(2+)-containing physiological conditions, treatment with 10(-4) mol/L CCh for 30 min induced heterologous desensitization to histamine and high K(+). The development of desensitization to histamine was interrupted by a transient resensitization at 1 min in a manner similar to that to CCh. In contrast, CCh-induced desensitization to high K(+) reached a peak at 1 min and was followed by a gradual resensitization up to a partial restoration at 30 min. 3. Under Ca(2+)-free conditions containing 0.2 mmol/L EGTA, treatment with 10(-4) mol/L CCh for 30 min failed to induce heterologous desensitization to either histamine or high K(+), whereas the CCh treatment developed homologous desensitization to CCh in a simple time-dependent manner without a resensitization phase. 4. These results suggest that cellular responsiveness to receptor agonists and non-receptor-mediated depolarizing stimulation is differentially regulated by Ca(2+)-dependent heterologous desensitization in smooth muscle.
Hishinuma
Shigeru
S
Department of Pharmacodynamics, Meiji Pharmaceutical University, Tokyo, Japan. hishi@my-pharm.ac.jp
Matsumoto
Yukio
Y
Sato
Ryo
R
Saito
Masaki
M
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002217:Carbachol; D002432:Cecum / Q000187:drug effects / Q000502:physiology; D018679:Cholinergic Agonists; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D018494:Histamine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000502:physiology
D018679:Cholinergic Agonists; D018494:Histamine Agents; D011969:Receptors, Histamine H1; D006632:Histamine; D002217:Carbachol; D011188:Potassium; D002118:Calcium