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Cardiovascular and behavioral responses to nicotinic agents administered intrathecally.
J Pharmacol Exp Ther. 1994 Jul; 270(1):150-8.JP

Abstract

We have examined the role of the spinal nicotinic receptors in mediating cardiovascular and behavioral responses in conscious rats. Intrathecal administration of nicotinic agonists to the lumbosacral region of the spinal cord caused a dose-dependent increase in systolic blood pressure, heart rate and a nociceptive (behavioral) response. The order of potencies for the pressor response was l-nicotine > or = cytisine > N-methylcarbamylcholine > or = dimethylphenylpiperazinium > d-nicotine. However, cytisine was the most potent in producing the heart rate increase and nociceptive response. Unlike the other agonists, cytisine also exhibited marked desensitization of the three responses upon repeated administration. The effects of nicotine were antagonized in a dose-dependent fashion by mecamylamine, hexamethonium, alpha-lobeline, dihydro-beta-erythroidine and methyllycaconitine. By contrast, cytisine-induced responses were blocked effectively by mecamylamine and methyllycaconitine, but not by alpha-lobeline or dihydro-beta-erythroidine. However, when alpha-lobeline or dihydro-beta-erythroidine antagonism of the pressor response to cytisine was monitored during the initial minute following intrathecal administration, both antagonists significantly inhibited the response. The competitive ganglionic blocker, trimethaphan, or the elapid alpha-toxin, alpha-bungarotoxin, when administered intrathecally, had no effect on nicotine- or cytisine-elicited responses. The cardiovascular responses to intrathecal nicotine and cytisine have two components. The first is likely mediated through direct sympathetic output and desensitizes rapidly to cytisine, the second is coupled indirectly to the nociceptive response and shows a diminished capacity for rapid desensitization. Agonist and antagonist specificities indicate that the spinal nicotinic receptor differs from those in ganglia and those characterized in brain to date. Although antagonist specificity of the blockade of nicotine and cytisine elicited responses differ, this may be due to the unique desensitization capacity of cytisine rather than an action mediated by distinct receptor subtypes.

Authors+Show Affiliations

Department of Pharmacology, University of California, San Diego, La Jolla.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8035311

Citation

Khan, I M., et al. "Cardiovascular and Behavioral Responses to Nicotinic Agents Administered Intrathecally." The Journal of Pharmacology and Experimental Therapeutics, vol. 270, no. 1, 1994, pp. 150-8.
Khan IM, Taylor P, Yaksh TL. Cardiovascular and behavioral responses to nicotinic agents administered intrathecally. J Pharmacol Exp Ther. 1994;270(1):150-8.
Khan, I. M., Taylor, P., & Yaksh, T. L. (1994). Cardiovascular and behavioral responses to nicotinic agents administered intrathecally. The Journal of Pharmacology and Experimental Therapeutics, 270(1), 150-8.
Khan IM, Taylor P, Yaksh TL. Cardiovascular and Behavioral Responses to Nicotinic Agents Administered Intrathecally. J Pharmacol Exp Ther. 1994;270(1):150-8. PubMed PMID: 8035311.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiovascular and behavioral responses to nicotinic agents administered intrathecally. AU - Khan,I M, AU - Taylor,P, AU - Yaksh,T L, PY - 1994/7/1/pubmed PY - 1994/7/1/medline PY - 1994/7/1/entrez SP - 150 EP - 8 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 270 IS - 1 N2 - We have examined the role of the spinal nicotinic receptors in mediating cardiovascular and behavioral responses in conscious rats. Intrathecal administration of nicotinic agonists to the lumbosacral region of the spinal cord caused a dose-dependent increase in systolic blood pressure, heart rate and a nociceptive (behavioral) response. The order of potencies for the pressor response was l-nicotine > or = cytisine > N-methylcarbamylcholine > or = dimethylphenylpiperazinium > d-nicotine. However, cytisine was the most potent in producing the heart rate increase and nociceptive response. Unlike the other agonists, cytisine also exhibited marked desensitization of the three responses upon repeated administration. The effects of nicotine were antagonized in a dose-dependent fashion by mecamylamine, hexamethonium, alpha-lobeline, dihydro-beta-erythroidine and methyllycaconitine. By contrast, cytisine-induced responses were blocked effectively by mecamylamine and methyllycaconitine, but not by alpha-lobeline or dihydro-beta-erythroidine. However, when alpha-lobeline or dihydro-beta-erythroidine antagonism of the pressor response to cytisine was monitored during the initial minute following intrathecal administration, both antagonists significantly inhibited the response. The competitive ganglionic blocker, trimethaphan, or the elapid alpha-toxin, alpha-bungarotoxin, when administered intrathecally, had no effect on nicotine- or cytisine-elicited responses. The cardiovascular responses to intrathecal nicotine and cytisine have two components. The first is likely mediated through direct sympathetic output and desensitizes rapidly to cytisine, the second is coupled indirectly to the nociceptive response and shows a diminished capacity for rapid desensitization. Agonist and antagonist specificities indicate that the spinal nicotinic receptor differs from those in ganglia and those characterized in brain to date. Although antagonist specificity of the blockade of nicotine and cytisine elicited responses differ, this may be due to the unique desensitization capacity of cytisine rather than an action mediated by distinct receptor subtypes. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8035311/Cardiovascular_and_behavioral_responses_to_nicotinic_agents_administered_intrathecally_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8035311 DB - PRIME DP - Unbound Medicine ER -