title: Caffeine and carbonyl cyanide m-chlorophenylhydrazone increased evoked and spontaneous release of luteinizing hormone-releasing hormone from intact presynaptic terminals.
abstract: In bullfrog sympathetic ganglia, the ryanodine-sensitive Ca2+ store and mitochondria modulate [Ca2+] within nerve terminals. We used caffeine (10 mM) and carbonyl cyanide m-chlorophenylhydrazone (10 microM) to assess how these Ca2+ stores affect release of a neuropeptide, luteinizing hormone-releasing hormone, from these nerve terminals. Release of luteinizing hormone-releasing hormone was evoked by electrical stimulation to presynaptic nerves and was monitored as a late slow excitatory postsynaptic potential in ganglionic neurons. Caffeine increased release of luteinizing hormone-releasing hormone similarly whether the release was evoked by 4 or 20 Hz stimulations (by 2.7 +/- 1.1- and 3.2 +/- 0.9-fold, mean +/- S.E.M., n = 27, respectively). Carbonyl cyanide m-chlorophenylhydrazone augmented release of luteinizing hormone-releasing hormone evoked by 4 Hz stimulation much more strongly (by 11.8 +/- 1.8-fold) than it increased the release evoked by 20 Hz stimulation (by 3.6 +/- 1.3-fold, n = 25). We detected spontaneous release of luteinizing hormone-releasing hormone as a slow hyperpolarization in response to a brief application of an antagonist to the receptors for luteinizing hormone-releasing hormone in 65% (34 of 52) and 39% (11 of 28) of the ganglionic B and C neurons, respectively. Caffeine increased spontaneous release of luteinizing hormone-releasing hormone by 2.3 +/- 0.7-fold (n = 6) whereas carbonyl cyanide m-chlorophenylhydrazone increased this release by 4.27- and 1.76-fold (n = 2). Facilitation of Ca2+ release from the intracellular store by caffeine and inhibition of mitochondrial Ca2+ removal by carbonyl cyanide m-chlorophenylhydrazone increased spontaneous as well as evoked release of luteinizing hormone-releasing hormone. Moreover, caffeine increments of evoked release did not depend on the firing frequency of the nerve whereas carbonyl cyanide m-chlorophenylhydrazone augmentations of evoked release strongly depended on the firing frequency.
authors.affiliation: Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637, USA.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Cao
authors.forename: Y Y
authors.initials: YY
authors.lastname: Peng
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011892:Rana catesbeiana; D013268:Stimulation, Chemical; D014475:Uncoupling Agents / Q000494:pharmacology*
chemical_list: D000697:Central Nervous System Stimulants; D014475:Uncoupling Agents; D007987:Gonadotropin-Releasing Hormone; D002110:Caffeine; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000109:Acetylcholine; D002118:Calcium