The depolarizing action of 5-hydroxytryptamine on rabbit isolated preganglionic cervical sympathetic nerves

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Abstract
This study describes a depolarizing action of 5-hydroxytryptamine (5-HT) on rabbit isolated preganglionic cervical sympathetic nerves using an extracellular recording technique. From cumulative concentration-response curves for 5-HT (1 μmol/1-1 mmol/1), the mean maximal depolarization was shown to be 277 ± 32 μV and EC50 was 9.4 μmol/l(6.5–13.6 μmol/l, geometric mean, 95% confidence limits, n = 42). The responses to 5-HT displayed marked tachyphylaxis. When cumulative concentration-response curves to 5-HT and 2-methyl-5-HT were determined in the same preparations (n = 4), the mean maximal response to 5-HT was 519 ± 167 μV, EC50 32.2 μmol/l (8.8–118 μmol/l) and the mean maximal response to 2-methyl-5-HT was 317 ± 63 μV, EC50 35.1 μmol/l (12.9–95.5 μmol/l, geometric means, 95 % confidence limits). The action of selective 5-HT antagonists was tested on repeated cumulative concentration-response curves to 5-HT. Neither methiothepin (0.1–1 μmol/l, n = 3) nor ketanserin (0.1–1 μmol/l, n = 3) had an action on 5-HT responses. The selective 5-HT3 antagonists MDL 72222, ICS 205-930 and SDZ 206–830 were all potent antagonists of the 5-HT depolarizations. The action of these antagonists was quantified by determining the apparent pA2 from the dose ratios and a Schild plot. For MDL 72222 (1 nmol/1-0.1 μmol/l), the apparent pA2 was 9.1 ± 0.1 (n = 12), Schild plot: 9.2; for ICS 205–930 (0.1 nmol/l–3 nmol/1), the apparent pA2 was 10.4 ± 0.1 (n = 11), Schild plot 10.3, and for SDZ 206–830 (0.03 nmol/l-1 nmol/1), the apparent pA2 was 11.2 ± 0.1 (n = 12), Schild plot 11.2. 5-HT depolarizations were unaffected by hexamethonium (0.5 mmol/1). 5-HT depolarizations were reduced by superfusion with both Na-free (42 ± 8% of controls, n = 4) and Na/Ca-free media (35 ± 7% of controls, n = 4). It is concluded that 5-HT depolarizations of rabbit preganglionic cervical sympathetic nerve are mediated by 5-HT3 receptors. The data with selective 5-HT3 receptor antagonists suggest that the receptor profile may be more like that for the 5-HT3 receptor on the terminals of sympathetic nerves than that for the 5-HT3 receptor on the soma of superior cervical ganglion cells or on vagal afferent neurones.