Potentiation of nicotinic transmission in the rat superior cervical sympathetic ganglion: effects of cyclic GMP and nitric oxide generators.
The efficacy of nicotinic transmission in the rat superior cervical ganglion in vitro (24-26 degrees C) was estimated by extracellular recording of the postganglionic compound action potential response to stimulation of the preganglionic nerve at a slow rate (one shock every 60 s). Atropine (2 microM) was included to block muscarinic transmission, and hexamethonium (200-250 microM) was used to produce a submaximal response sensitive to potentiation and inhibition of nicotinic transmission. Upon exposure to 1-100 microM 8-bromo-guanosine 3',5'-cyclic monophosphate (8-Br-cGMP), nicotinic transmission was potentiated by 6 +/- 1% (n = 4) to 89 +/- 5% (n = 5) in a dose-dependent manner. 8-Bromo-adenosine 3',5'-cyclic monophosphate (8-Br-cAMP, 10-100 microM) also potentiated nicotinic transmission (3.8 +/- 0.3% (n = 3) to 43 +/- 4% (n = 3)). However, 8-Br-cGMP was at least 2-fold more effective than 8-Br-cAMP. Sodium nitroprusside (0.1 microM to 1 mM) and sodium azide (0.1-100 microM) were used to stimulate the formation of endogenous cGMP52. Nicotinic transmission was potentiated by these substances also. The response was increased by 3.4 +/- 0.7% (n = 4) to 32 +/- 2% (n = 5) upon exposure to 0.1-100 microM sodium nitroprusside, and by 5.5 +/- 0.9% (n = 3) to 18 +/- 4% (n = 4) upon exposure to 0.1-100 microM sodium azide. Ferricyanide ion (10-100 microM) appeared to be ineffective, as would be expected if the effect of nitroprusside was due to the nitric oxide rather than the cyanide or ferric moieties.(ABSTRACT TRUNCATED AT 250 WORDS)
Briggs
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Neuroscience Research, Abbott Laboratories, Abbott Park, IL 60064.
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001386:Azides / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects*; D019810:Sodium Azide; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
D001386:Azides; D011978:Receptors, Nicotinic; D009599:Nitroprusside; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D019810:Sodium Azide; D006152:Cyclic GMP