PT  - JOURNAL ARTICLE
AU  - Damaj, M I
AU  - Welch, S P
AU  - Martin, B R
TI  - Involvement of calcium and L-type channels in nicotine-induced antinociception.
DP  - 1993 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1330--1338
VI  - 266
IP  - 3
4099  - http://jpet.aspetjournals.org/content/266/3/1330.short
4100  - http://jpet.aspetjournals.org/content/266/3/1330.full
SO  - J Pharmacol Exp Ther1993 Sep 01; 266
AB  - The nature of the signaling process activated by neuronal nicotinic receptors has not been fully defined; however, several recent studies have implicated the involvement of calcium ion fluxes in the response to nicotine on a cellular level. Alteration of nicotine-induced antinociception in mice after systemic administration was therefore investigated in the presence of several drugs that increase intracellular calcium. Calcium, (+/-)-BAYK 8644, thapsigargin, glyburide and A23187 administered intrathecally (i.t.) were found to enhance nicotine-induced antinociception by shifting its dose-response curve to the left. Conversely, i.t. administration of agents which decrease intracellular calcium, such as EGTA and alpha-calcitonin gene-related peptide, blocked nicotine-induced antinociception. These findings support a role for spinal intracellular calcium in the pharmacological effects of nicotine. Additionally, blockade of antinociception by nimodipine and nifedipine indicates that a L-type calcium channel is involved in nicotine's effect. However, nicotine did not compete for [3H] nitrendipine binding. Intrathecal administration of mecamylamine, a nicotinic antagonist, resulted in a blockade of antinociception produced by the i.t. injection of thapsigargin, A23187, calcium and (+/-)-BAYK 8644. The mechanism of mecamylamine's antagonism of nicotine is uncertain. However, these results suggest that mecamylamine blocks the effects of drugs which increase intracellular calcium by either a modulation of intracellular calcium-dependent mechanisms or a blockade of calcium channels. Thus, mecamylamine could modulate a calcium signaling process secondary to receptor activation resulting in blockade of antinociception produced by diverse agents.