Nitric oxide acts independently of cGMP to modulate capacitative Ca(2+) entry in mouse parotid acini.
Carbachol- and thapsigargin-induced changes in cGMP accumulation were highly dependent on extracellular Ca(2+) in mouse parotid acini. Inhibition of nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC) resulted in complete inhibition of agonist-induced cGMP levels. NOS inhibitors reduced agonist-induced Ca(2+) release and capacitative Ca(2+) entry, whereas the inhibition of sGC had no effect. The effects of NOS inhibition were not reversed by 8-bromo-cGMP. The NO donor GEA-3162 increased cGMP levels blocked by the inhibition of sGC. GEA-3162-induced increases in Ca(2+) release from ryanodine-sensitive stores and enhanced capacitative Ca(2+) entry, both of which were unaffected by inhibitors of sGC but reduced by NOS inhibitors. Results support a role for NO, independent of cGMP, in agonist-mediated Ca(2+) release and Ca(2+) entry. Data suggest that agonist-induced Ca(2+) influx activates a Ca(2+)-dependent NOS, leading to the production of NO and the release of Ca(2+) from ryanodine-sensitive stores, providing a feedback loop by which store-depleted Ca(2+) channels are activated.
Watson
E L
EL
Department of Oral Biology, University of Washington, Seattle, Washington 98195, USA. ewatson@u.washington.edu
Jacobson
K L
KL
Singh
J C
JC
Ott
S M
SM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010306:Parotid Gland / Q000378:metabolism*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D020030:Nitric Oxide Donors; D019837:Ryanodine Receptor Calcium Release Channel; D009569:Nitric Oxide; D019284:Thapsigargin; D009116:Muscarine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP; D002118:Calcium