Effects of the antagonists MDL 72222 and ketanserin on responses of cat carotid body chemoreceptors to 5‐hydroxytiyptamine

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Abstract
1 The effects of intracarotid (i.c.) injections of 5-hydroxytryptamine (5-HT; 1–50 μg) on carotid chemoreceptor activity recorded from the carotid sinus nerve have been studied in anaesthetized cats. 2 Three separate components in the complex response of the chemoreceptors to injected 5-HT were identified. Firstly, a transient burst of activity was obtained during the injection period in 56% of the recordings. Secondly, in all the recordings a period of chemodepression commenced a few seconds after completing the injection and was usually dose-related. Thirdly, a delayed longer-lasting chemoexcitation occurred in many experiments, concomitant with a fall in systemic blood pressure. 3 The neuronal 5-HT receptor antagonist MDL 72222 (10–100 μg kg−1, i.c.) virtually abolished the transient chemoexcitation evoked during 5-HT injections and also significantly increased the mean ID50 for 5-HT-induced chemodepression; in 37% of recordings 5-HT caused a dose-related chemoexcitation after the high dose of MDL 72222. Neither the delayed chemoexcitation nor the hypotension caused by 5-HT were much affected by the antagonist. MDL 72222 itself had a biphasic effect on chemosensory discharge, causing depression followed by a delayed excitation. 4 The 5-HT2-receptor antagonist ketanserin (100 μg kg−1, i.c.) had no appreciable effect on the transient chemoexcitation evoked during 5-HT injections and caused a slight but significant increase in the mean ID50 for 5-HT-induced chemodepression. The delayed chemoexcitation and accompanying hypotension associated with 5-HT were both substantially reduced or abolished by the antagonist. Ketanserin itself caused a short-lasting period of chemoexcitation. 5 All the effects of injected 5-HT on chemosensory discharge could be abolished by the combination of MDL 72222 and ketanserin (100 μg kg−1, i.c.). 6 Neither MDL 72222 nor ketanserin had any significant effect upon the response of the carotid chemoreceptors to hypoxia. The rate at which discharge increased, and also the steady-state discharge before and during hypoxia, were unaffected by the antagonists, alone or in combination. 7 At least two types of 5-HT receptor appeared to be involved in the response of carotid body chemoreceptors to 5-HT. Transient excitation and chemodepression wer*** mediated via MDL 72222-sensitive (peripheral neuronal) receptors whereas the delayed chemoexcitation and associated hypotension involved a ketanserin-sensitive, presumably 5-HT2-, receptor. It appears unlikely that 5-HT plays a crucial role in chemoreception.