title: Sinusoidal oscillations in intracellular calcium requiring negative feedback by protein kinase C.
abstract: Stimulation of mouse lacrimal acinar cells with submaximal concentrations of the muscarinic agonist, methacholine, resulted in an increase in intracellular calcium ([Ca2+]i), which took the form of sinusoidal oscillations. These oscillations were relatively constant (approximately 4-5/min) regardless of the methacholine concentration, suggesting that the oscillations arise from an oscillating negative feedback in the signal transduction pathway. This negative feedback appears to involve oscillations in protein kinase C activity because the oscillations were prevented by activation, inhibition, or down-regulation of protein C. Activation of protein kinase C with phorbol esters inhibited the methacholine-induced [Ca2+]i signal and formation of the Ca2+ mobilizing messenger, inositol 1,4,5-trisphosphate. [Ca2+]i signals elicited by intracellular introduction of inositol phosphates did not oscillate and were not affected by activators or inhibitors of protein kinase C. Thus, the constant frequency [Ca2+]i oscillations appear to result from a negative feedback loop involving inhibition of inositol trisphosphate production by protein kinase C.
authors: Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709.
authors: G S
authors: GS
authors: Bird
authors: M F
authors: MF
authors: Rossier
authors: J F
authors: JF
authors: Obie
authors: J W
authors: JW
authors: Putney
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D005246:Feedback; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D010738:Type C Phospholipases; D002118:Calcium