Activation of nicotinic receptor-induced postsynaptic responses to luteinizing hormone-releasing hormone in bullfrog sympathetic ganglia via a Na ⁺ -dependent mechanism

Abstract

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 Ca 2؉ inf lux through either the nicotinic receptors or the voltage-gated Ca 2؉ channels because the release was increased moderately when the extracellular solution was changed into a Ca 2؉ -free solution that also contained Mg 2؉ (4 mM) and Cd 2؉ (200 M). The release did not depend on Ca 2؉ release from the intraterminal Ca 2؉ stores either because fura-2 f luorimetry showed extremely low Ca 2؉ elevation (Ϸ30 nM) in response to nicotine (30 nM). Moreover, nicotine evoked LHRH release when [Ca 2؉ ] elevation in the terminals was prevented by loading the terminals with 1,2-bis(2-aminophenoxy)ethane-N,N,N,Ntetraacetic 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 ؉ inf lux through the voltage-gated Na ؉ channels because the release was not affected by tetrodotoxin (1-50 M) plus Cd 2؉ (200 M). Thus, nicotine at very low concentrations induced LHRH release via a Na ؉ -dependent, Ca 2؉ -independent mechanism.

Role played by sodium in activity‐dependent secretion of neurotrophins − revisited

“…Simasko, 1994; Chidekel et al . 1997; Rose & Ransom, 1997; Sidky & Baimbridge, 1997; Cao & Peng, 1998; Taschenberger & Grantyn, 1998) blocked the high‐potassium‐, veratridine‐ and glutamate‐mediated NGF secretion from both hippocampal slices and NGF‐transfected hippocampal neurons (Blöchl & Thoenen, 1995). However, there is no experimental evidence that sodium influx mobilizes calcium from intracellular stores.…”

Gene regulation of α4β2 nicotinic receptors: microarray analysis of nicotine‐induced receptor up‐regulation and anti‐inflammatory effects

“…Our findings demonstrate that continuous exposure to nicotine suppresses the expression of PICs and chemokines (Table 1) via a4b2 receptors in ha4b2 SH-EP1 cells. The concentration of nicotine achieved in a smoker's brain is about 50-300 nM (Cao and Peng 1998;Paradiso and Steinbach 2003), which is sufficient to activate a4b2 receptors. Therefore, the putative neuroprotection seen in smokers may be due in part to an increase in high affinity a4b2 receptors and suppression of PICs via a4b2 nAChRs.…”

Peptide-Mediated Neurotransmission Takes Center Stage

“…LHRH-like peptide is co-released, its function putatively mediated by the LHRH-like peptide receptor. According to Cao and Peng (1998), docking of acetylcholine-filled vesicles occurs at the presynaptic active zone (AZ), whereas release of LHRH-like peptide occurs away from the AZ 15 .…”