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 luteinizing hormone-releasing hormone (LHRH) release, which was monitored as slow membrane depolarizations in the ganglionic neurons of bullfrog sympathetic ganglia. A nicotinic antagonist, d-tubocurarine chloride, completely 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 release. Moreover, this release was not caused by Ca2+ influx through either the nicotinic receptors or the voltage-gated Ca2+ channels because the release was increased moderately when the extracellular solution was changed into a Ca2+-free solution that also contained Mg2+ (4 mM) and Cd2+ (200 microM). The release did not depend on Ca2+ release from the intraterminal Ca2+ stores either because fura-2 fluorimetry showed extremely low Ca2+ elevation (approximately 30 nM) in response to nicotine (30 nM). Moreover, nicotine evoked LHRH release when [Ca2+] elevation in the terminals was prevented by loading the terminals with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid and fura-2. Instead, the nicotine-induced release required extracellular Na+ because substitution of extracellular NaCl with N-methyl-D-glucamine chloride completely 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 microM) plus Cd2+ (200 microM). Thus, nicotine at very low concentrations induced LHRH release via a Na+-dependent, Ca2+-independent mechanism.
Department of Pharmacological and Physiological Sciences, University of Chicago, 947 E. 58th Street, Chicago, IL 60637, USA.
Y J
YJ
Cao
Y Y
YY
Peng
D000818:Animals; D002118:Calcium / Q000502:physiology; D005728:Ganglia, Sympathetic / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000502:physiology*; D015640:Ion Channel Gating; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011892:Rana catesbeiana; D011978:Receptors, Nicotinic / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*; D013569:Synapses / Q000502:physiology*
D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D015222:Sodium Channels; D007987:Gonadotropin-Releasing Hormone; D009538:Nicotine; D002118:Calcium