Metabolism of inositol phosphates in parotid cells: implications for the pathway of the phosphoinositide effect and for the possible messenger role of inositol trisphosphate.
Rat parotid acinar cells were used to investigate the time course of formation and breakdown of inositol phosphates in response to receptor-active agents. In cells preincubated with [3H]inositol and in the presence of 10 mM LiCl (which blocks hydrolysis of inositol phosphate), methacholine (10(-4)M) caused a substantial increase in cellular content of [3H]inositol phosphate, [3H]inositol bisphosphate and [3H]inositol trisphosphate. Subsequent addition of atropine (10(-4) M) caused breakdown of [3H]inositol trisphosphate and [3H]inositol bisphosphate and little change in accumulated [3H]inositol phosphate. The data could be fit to a model whereby inositol trisphosphate and inositol bisphosphate are formed from phosphodiesteratic breakdown of phosphatidylinositol bisphosphate and phosphatidylinositol phosphate respectively, and inositol phosphate is formed from hydrolysis of inositol bisphosphate rather than from phosphatidyl-inositol. Consistent with this model was the finding that [3H]inositol trisphosphate and [3H]inositol bisphosphate levels were substantially increased in 5 sec while an increase in [3H]inositol phosphate was barely detectable at 60 sec. These results indicate that in the parotid gland the phosphoinositide cycle is activated primarily by phosphodiesteratic breakdown of the polyphosphoinositides rather than phosphatidyl-inositol. Also, the results show that formation of inositol trisphosphate is probably sufficiently rapid for it to act as a second messenger signalling internal Ca2+ release in this tissue.
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D007293:Inosine Triphosphate / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism* / Q000502:physiology; D007700:Kinetics; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D008954:Models, Biological; D010306:Parotid Gland / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013403:Sugar Phosphates / Q000378:metabolism*
D007295:Inositol Phosphates; D008688:Methacholine Compounds; D010716:Phosphatidylinositols; D013403:Sugar Phosphates; D016210:Methacholine Chloride; D007293:Inosine Triphosphate; D004247:DNA; D002118:Calcium