Regulation by clozapine of calcium handling by rat submandibular acinar cells.
The effect of clozapine on the intracellular concentration of calcium ([Ca2+](i)) in rat submandibular acinar cells was tested. By itself clozapine had no effect on the mobilization of intracellular pools of calcium or on the uptake of extracellular calcium. It inhibited the increase of the [Ca2+](i) in response to carbachol (half-maximal inhibitory concentrations, IC(50)=100nM) and to norepinephrine and epinephrine (IC(50)=10nM) without affecting the response to substance P, extracellular ATP or thapsigargin. Clozapine inhibited the uptake of extracellular calcium in response to epinephrine but not to substance P, ATP or thapsigargin. It also decreased the production of inositol phosphates elicited by epinephrine but not by substance P or fluoride. It is concluded that, by itself, clozapine has no effect on the [Ca2+](i) in rat salivary acinar cells. It selectively inhibits muscarinic and adrenergic receptors in the acinar plasma membrane.
Laboratoire de Biochimie et de Biologie Cellulaire, Institut de Pharmacie C.P. 205/3, Université libre de Bruxelles, B-1050 Brussels, Belgium.
S
S
Pochet
M
M
García-Marcos
M
M
Fernandez
A
A
Marino
J P
JP
Dehaye
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000493:pharmacokinetics; D002217:Carbachol / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D004347:Drug Interactions; D004837:Epinephrine / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013363:Submandibular Gland / Q000166:cytology* / Q000378:metabolism*
D014150:Antipsychotic Agents; D007295:Inositol Phosphates; D002217:Carbachol; D003024:Clozapine; D002118:Calcium; D009638:Norepinephrine; D004837:Epinephrine