ACTIVATION OF NICOTINIC RECEPTOR-INDUCED POSTSYNAPTIC RESPONSES TO LUTEINIZING-HORMONE-RELEASING HORMONE IN BULLFROG SYMPATHETIC-GANGLIA VIA A NA-DEPENDENT MECHANISM()

Nicotine at very low doses (5-30 nM) induced large amounts of luteiniz ing hormone-releasing hormone (LHRH) release, which was monitored as s low membrane depolarizations in the ganglionic neurons of bullfrog sym pathetic ganglia, A nicotinic antagonist, d-tubocurarine chloride, com pletely and reversibly blocked the nicotine-induced LHRH release, but it did not block the nerve-firing-evoked LHRH release. Thus, nicotine activated nicotinic acetylcholine receptors and produced LHRH release via a mechanism that is different from the mechanism for evoked releas e. Moreover, this release was not caused by Ca2+ influx through either the nicotinic receptors or the voltage-gated Ca2+ channels because th e release was increased moderately when the extracellular solution was changed into a Ca2+-free solution that also contained Mg2+ (4 mM) and Cd2+ (200 mu M). The release did not depend on Ca2+ release from the intraterminal Ca2+ stores either because fura-2 fluorimetry showed ext remely low Ca2+ elevation ( approximate to 30 nM) in response to nicot ine (30 nM), Moreover, nicotine evoked LHRH release when [Ca2+] elevat ion in the terminals was prevented by loading the terminals with 1,2-b is (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid and fura-2, Inst ead, the nicotine induced release required extracellular Na+ because s ubstitution of extracellular NaCl with N-methyl-D-glucamine chloride c ompletely blocked the release. The Na+-dependent mechanism was not via Na+ influx through the voltage-gated Na+ channels because the release was not affected by tetrodotoxin (1-50 mu M) plus Cd2+ (200 mu M). Th us, nicotine at very low concentrations induced LHRH release via a Na-dependent, Ca2+-independent mechanism.