Enhancement by 5‐hydroxytryptamine and analogues of desensitization of neuronal and muscle nicotinic receptors expressed in Xenopus oocytes

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Abstract
1 The action of 5-hydroxytryptamine (5-HT) on neuronal and muscle nicotinic acetylcholine receptors (nicotinic AChR) expressed in Xenopus oocytes was studied. 2 5-HT enhanced the rate of desensitization of the acetylcholine (ACh) current response in all receptor subtypes investigated (muscle, αβ2γδ and α4β2), acting in a dose-dependent manner. 3 5-HT also reduced the peak current elicited by ACh in a dose-dependent manner. The IC50 value for the muscle type receptor was 227 ± 0.44 μm, and 166 ± 0.47 μm and 283 ± 0.28 μm for the combinations αβ2γ and α4β2 respectively. 4 The effect of 5-HT on the responses to ACh (10 μm) was found to be independent of membrane voltage over the range tested (−80 to −10 mV), and to be readily reversed by washout. 5 The action of 5-HT could be mimicked by structurally similar molecules. The homologue tryptamine was less potent than 5-HT in blocking the ACh current, with an IC50 of 1.0 ± 0.02 mM. Ketanserin, a 5-HT2 receptor antagonist, was more potent than 5-HT, the IC50 being 49.0 ± 1.4 μm. 6 We postulate that a highly conserved portion of the tertiary structure of nicotinic AChRs, which includes some part of the ACh binding site, has affinity for 5-HT and structural analogues.