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The depolarizing action of 5‐hydroxytryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205–930
Author(s) -
Round Alison,
Wallis D.I.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb10227.x
Subject(s) - depolarization , superior cervical ganglion , chemistry , blockade , antagonist , serotonin , endocrinology , medicine , sucrose gap , cervical ganglia , receptor , biochemistry
1 Depolarizing responses to 5‐hydroxytryptamine (5‐HT) were recorded from rabbit nodose (NG) and superior cervical (SCG) ganglia using the sucrose‐gap technique. The antagonist potency and selectivity of ICS 205–930 ([3α‐tropanyl]‐1H‐indole‐3‐carboxylic acid ester) were investigated. 2 In NG, 5‐HT (5 to 80 nmol) evoked depolarizations of graded amplitude. The ED 50 was 18.2 (10.9–30.5) nmol (geometric mean, 95% confidence limits). Responses were blocked surmountably by ICS 205–930, 10 −11 and 10 −10 M, the threshold for blockade being below 10 −11 M. Parallel, rightward shifts in dose‐response curves were seen with these concentrations of antagonist, but at higher concentrations (10 −9 and 10 −8 M) there was a further rightward shift with reduction in slope and maximum of the curves. 3 In SCG, where 5‐HT (20 to 320 nmol) evoked depolarizations of graded amplitude and the ED 50 was 55.8 (22.3–139.6) nmol (geometric mean, 95% confidence limits), ICS 205–930 had a similar inhibitory effect to that observed in NG. 4 The apparent pA 2 values for the surmountable blockade produced by ICS 205–930 at concentrations of 10 −11 and 10 −10 M were 10.2 ± 0.2 for NG and 10.4 ± 0.1 for SCG (means ± s.e. mean). 5 ICS 205–930 was selective in its action since it had no effect on dimethylphenylpiperazinium (DMPP) responses in either ganglion or on GABA responses in NG. 6 This study provides quantitative evidence on the blocking action of ICS 205–930 at neuronal 5‐HT receptors using a technique that allows the depolarizing responses evoked by the amine to be directly recorded.