Role of protein kinase C in the regulation of inositol phosphate production and Ca2+ mobilization evoked by ATP and acetylcholine in rat lacrimal acini.
Stimulation of rat lacrimal acinar cells with ATP and acetylcholine (ACh) induced a rapid accumulation of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and its degradation products, resulting in an initial release of Ca2+ from intracellular stores. However, after pretreating the acini with U73122 no increase in the intracellular free Ca2+ concentration ([Ca2+]i) or Ins(1,4,5)P3 production was observed. A short pretreatment with the phorbol ester 4-beta-phorbol-12-beta-myristate-13-alpha-acetate (PMA) significantly attenuated the ATP- and ACh-induced increase in [Ca2+]i and overall inositol phosphate production. In contrast, staurosporine enhanced Ins(1,4,5)P3 and inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] production and [Ca2+]i above control values in ATP- and ACh-stimulated cells. Stimulation of phospholipase C by ionomycin-evoked changes in [Ca2+]i were unaltered by pretreatment with staurosporine and PMA. The data show that a change in protein kinase C activity during cell stimulation affects the inositol phosphate metabolism and thereby the cellular Ca2+ signalling processes in lacrimal acinar cells.
Gromada
J
J
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
Jørgensen
T D
TD
Dissing
S
S
D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D007294:Inositol / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D007765:Lacrimal Apparatus / Q000502:physiology*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine; D013997:Time Factors
D000470:Alkaloids; D007294:Inositol; D015759:Ionomycin; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D019311:Staurosporine; D000109:Acetylcholine; D002118:Calcium