title: Relationship between nitric oxide- and calcium-dependent signal transduction pathways in growth hormone release from dispersed goldfish pituitary cells.
abstract: Nitric oxide (NO) and Ca(2+) are two of the many intracellular signal transduction pathways mediating the control of growth hormone (GH) secretion from somatotropes by neuroendocrine factors. We have previously shown that the NO donor sodium nitroprusside (SNP) elicits Ca(2+) signals in identified goldfish somatotropes. In this study, we examined the relationships between NO- and Ca(2+)-dependent signal transduction mechanisms in GH secretion from primary cultures of dispersed goldfish pituitary cells. Morphologically identified goldfish somatotropes stained positively for an NO-sensitive dye indicating they may be a source of NO production. In 2h static incubation experiments, GH release responses to the NO donor S-nitroso-N-acetyl-d,l-penicillamine (SNAP) were attenuated by CoCl2, nifedipine, verapamil, TMB-8, BHQ, and KN62. In column perifusion experiments, the ability of SNP to induce GH release was impaired in the presence of TMB-8, BHQ, caffeine, and thapsigargin, but not ryanodine. Caffeine-elicited GH secretion was not affected by the NO scavenger PTIO. These results suggest that NO-stimulated GH release is dependent on extracellular Ca(2+) availability and voltage-sensitive Ca(2+) channels, as well as intracellular Ca(2+) store(s) that possess BHQ- and/or thapsigargin-inhibited sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPases, as well as TMB-8- and/or caffeine-sensitive, but not ryanodine-sensitive, Ca(2+)-release channels. Calmodulin kinase-II also likely participates in NO-elicited GH secretion but caffeine-induced GH release is not upstream of NO production. These findings provide insights into how NO actions many integrate with Ca(2+)-dependent signalling mechanisms in goldfish somatotropes and how such interactions may participate in the GH-releasing actions of regulators that utilize both NO- and Ca(2+)-dependent transduction pathways.
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada. Electronic address: john.chang@ualberta.ca.
authors.forename: John P
authors.initials: JP
authors.lastname: Chang
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
authors.forename: Grant R
authors.initials: GR
authors.lastname: Sawisky
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Davis
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Pemberton
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
authors.forename: Aja M
authors.initials: AM
authors.lastname: Rieger
authors.affiliation: Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada; Department of Agriculture, Forestry and Nutritional Science, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Barreda
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006054:Goldfish / Q000378:metabolism*; D013006:Growth Hormone / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000697:Central Nervous System Stimulants; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D002110:Caffeine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019284:Thapsigargin; D013006:Growth Hormone; D009543:Nifedipine; D002118:Calcium
keywords: Caffeine; Calmodulin kinase; Extracellular and intracellular Ca(2+)-dependence; NO donor and scavenger; SERCA and calcium release channels