Nitric oxide and cGMP activate Ca2+-release processes in rat parotid acinar cells.
We characterized the enzymic properties of ADP-ribosyl cyclase in rat parotid acinar cells by using a fluorescence technique. ADP-ribosyl cyclase is capable of synthesizing the Ca2+ -mobilizing nucleotide cADP-ribose (cADPR) from NAD(+) and has previously been shown to be regulated by cGMP via a cGMP-dependent protein kinase (G kinase). We therefore investigated whether NO/cGMP-activated pathways are present in rat parotid acinar cells and whether NO/cGMP signalling exerts control over cellular Ca2+ signalling processes. Our results showed that stimulation of acinar cells with adrenaline, isoproterenol, substance P and NO resulted in a rise in the [cGMP]. In addition, NO induced a release of Ca2+ from intracellular ryanodine-sensitive stores via a cGMP/G-kinase-mediated process. Thus our data reveal that a rise in [cGMP], caused by either neurotransmitter or NO activation, activates a G kinase, which in turn controls Ca2+ release from ryanodine-sensitive stores. Since parotid acinar cells possess ADP-ribosyl cyclase activity, we propose a model in which cADPR is the link between NO/cGMP signalling pathways and release of Ca2+ from ryanodine-sensitive stores.
Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 N, Denmark.
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D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology*; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D010306:Parotid Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D012433:Ryanodine / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D015703:Antigens, CD; D000943:Antigens, Differentiation; D008562:Membrane Glycoproteins; D012433:Ryanodine; D009569:Nitric Oxide; D036541:ADP-ribosyl Cyclase; C498156:Cd38 protein, rat; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1; D006152:Cyclic GMP; D002118:Calcium