The effects of substance P and carbachol on inositol tris- and tetrakisphosphate formation and cytosolic free calcium in rat parotid acinar cells. A correlation between inositol phosphate levels and calcium entry.
Both substance P and carbachol produced increases in inositol tris- and tetrakisphosphate and increased cytosolic free [Ca2+] in dispersed parotid acinar cells loaded with fura-2. The increase in [Ca2+]i in response to each agonist was due to a combination of mobilization of internal Ca2+ and entry of extracellular Ca2+. Kinetic studies of the initial response to substance P, and measurement of peak [Ca2+]i, demonstrated that the initial rapid rise in [Ca2+]i was due to both internal release and entry of Ca2+. Substance P could evoke a greater initial increase in [Ca2+]i and inositol trisphosphate than could carbachol. However, after 1 min in the presence of external Ca2+, the maintained [Ca2+]i level in response to substance P was considerably smaller than that seen with carbachol, an effect apparently due to homologous desensitization of the substance P receptor. The two agonists each produced a similar 4-5-fold increase in inositol tetrakisphosphate levels within 30 s; this level was maintained in the presence of carbachol, but decreased with substance P. Similarly, the level of inositol (1,4,5)-trisphosphate decreased after prolonged incubation with substance P. Thus, the maintained level of [Ca2+]i, and by deduction Ca2+ entry, correlated with the levels of inositol (1,4,5)-trisphosphate and inositol tetrakisphosphate; a result consistent with a possible role for these inositol phosphates in the control of receptor-mediated Ca2+ channels.
D000818:Animals; D001572:Benzofurans / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000096:biosynthesis*; D007700:Kinetics; D010306:Parotid Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D013373:Substance P / Q000494:pharmacology*; D013403:Sugar Phosphates / Q000096:biosynthesis*
D001572:Benzofurans; D002614:Chelating Agents; D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013373:Substance P; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D002118:Calcium; D016257:Fura-2