Journal article
Cross-regulation between colocalized nicotinic acetylcholine and 5-HT3 serotonin receptors on presynaptic nerve terminals
Acta pharmacologica Sinica, v 30(6), pp 788-794
01 Jun 2009
PMID: 19498419
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Aim: Substantial colocalization of functionally independent alpha 4 nicotinic acetylcholine receptors and 5-HT3 serotonin receptors on presynaptic terminals has been observed in brain. The present study was aimed at addressing whether nicotinic acetylcholine receptors and 5-HT3 serotonin receptors interact on the same presynaptic terminal, suggesting a convergence of cholinergic and serotonergic regulation.
Methods: Ca2+ responses in individual, isolated nerve endings purified from rat striatum were measured using confocal imaging.
Results: Application of 500 nmol/L nicotine following sustained stimulation with the highly selective 5-HT3 receptor agonist m-chlorophenylbiguanide at 100 nmol/L resulted in markedly reduced Ca2+ responses (28% of control) in only those striatal nerve endings that originally responded to m-chlorophenylbiguanide. The cross-regulation developed over several minutes. Presynaptic nerve endings that had not responded to m-chlorophenylbiguanide, indicating that 5-HT3 receptors were not present, displayed typical responses to nicotine. Application of m-chlorophenylbiguanide following sustained stimulation with nicotine resulted in partially attenuated Ca2+ responses (49% of control). Application of m-chlorophenylbiguanide following sustained stimulation with m-chlorophenylbiguanide also resulted in a strong attenuation of Ca2+ responses (12% of control), whereas nicotine-induced Ca2+ responses following sustained stimulation with nicotine were not significantly different from control.
Conclusion: These results indicate that the presynaptic Ca2+ increases evoked by either 5-HT3 receptor or nicotinic acetylcholine receptor activation regulate subsequent responses to 5-HT3 receptor activation, but that only 5-HT3 receptors cross-regulate subsequent nicotinic acetylcholine receptor-mediated responses. The findings suggest a specific interaction between the two receptor systems in the same striatal nerve terminal, likely involving Ca2+-dependent intracellular pathways that regulate these signaling systems at one or more levels.
Metrics
Details
- Title
- Cross-regulation between colocalized nicotinic acetylcholine and 5-HT3 serotonin receptors on presynaptic nerve terminals
- Creators
- John J. Dougherty - Drexel UniversityRobert A. Nichols - Drexel UniversityDeborah J Clegg
- Publication Details
- Acta pharmacologica Sinica, v 30(6), pp 788-794
- Publisher
- ACTA PHARMACOLOGICA SINICA
- Number of pages
- 7
- Grant note
- R01 AG021586; AG 21586 / NIA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01AG021586 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Obstetrics and Gynecology
- Web of Science ID
- WOS:000266916900015
- Scopus ID
- 2-s2.0-67549118802
- Other Identifier
- 991019357768604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary
- Pharmacology & Pharmacy