The effect of 5-HT and selective 5-HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro

Albert, Anthony P. ORCID: https://orcid.org/0000-0002-3596-9634, Spyer, K. Michael and Brooks, Penelope A. (1996) The effect of 5-HT and selective 5-HT receptor agonists and antagonists on rat dorsal vagal preganglionic neurones in vitro. British Journal of Pharmacology, 119 (3). pp. 519-526. ISSN 0007-1188

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Abstract

1. Whole-cell patch-clamp recordings were made from 142 visually identified rat dorsal vagal preganglionic neurones (DVMs). Applications of 5-hydroxytryptamine (5-HT, 20 μM, 2 min) elicited a slow depolarization (8.2 ± 0.5 mV, n = 59) in 95% of the cells tested, accompanied by an increase in excitability. In (68%) of DVMs the depolarization was associated with an increase in apparent membrane resistance (R(m), 22.7 ± 2.2%). These depolarizations and increases in R(m) (14.3 ± 2.6%, n = 8) were maintained in a medium which blocked synaptic transmission. 2. The response to 5-HT was associated with a reversal potential (E(rev)) of -91 ± 1 mV at an extracellular K+ concentration ([K+]0) of 4.2 mM. This correlated well with the K+ equilibrium potential (E(K) = -89 mV). 3. The depolarizing effect of 5-HT was attenuated by the 5-HT(2A/2C) receptor antagonists, ketanserin (1 μM), LY 53,857 (1 μM) and the 5-HT(1A/2A) receptor antagonist, spiperone (1 μM). The 5-HT(1A) receptor antagonist, pindobind 5-HT(1A) (5 μM), had no effect on the depolarizing response to 5-HT. 4. The effect of 5-HT was mimicked by the 5-HT(2A/2C) receptor agonist, α-methyl-5-HT (50 μM), the 5-HT3 receptor agonist, 5-carboxamidotryptamine (20 μM) and the putative 5-HT4 agonist, 5-methyoxytryptamine (50 μM). The selective 5-HT4 receptor antagonist, GR113808, had no effect on the depolarizing effect of 5-HT or 5-MEOT on DVMs. 5. The 5-HT3 antagonists, MDL 72222 (10 μM) and ICS-205-930 (1 and 10 μM), partially reduced the effect of 5-HT. The 5-HT3 receptor agonist, 2-methyl-5-HT (100-300 μM), excited a proportion of neurones tested (56%) by evoking a depolarizing and/or an increase in postsynaptic potentials (p.s.ps). 6. These results are consistent with direct, postsynaptic actions of 5-HT on DVMs via 5-HT(2A) receptors, being mediated, in part, by the reduction of K+ conductance.

Item Type: Article
Uncontrolled Keywords: 5-ht,5-ht(2a) receptor subtype,dorsal vagal preganglionic neurones,potassium channels,whole-cell patch-clamp recording,pharmacology ,/dk/atira/pure/subjectarea/asjc/3000/3004
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 29 Oct 2024 09:30
Last Modified: 03 Nov 2024 07:31
URI: https://ueaeprints.uea.ac.uk/id/eprint/97286
DOI: 10.1111/j.1476-5381.1996.tb15702.x

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