A quantitative pharmacological study of some putative neurotransmitters in the carotid body of the cat and the rabbit
Afferent chemoreceptor activity was recorded from the peripheral cut end of the sinus nerve in anaesthetized cats and rabbits. It was found that intracarotid injection of dopamine inhibited spontaneous chemoreceptor activity in both species. 5~Hydroxytryptamine evoked a brief excitation followed by inhibition of discharge in both species. In cats, apomorphine caused a prolonged inhibition of chemoreceptor activity. Following administration of a~flupenthixol or haloperidol in cats and a-f1upenthixol in rabbits, dopamine no longer evoked an inhibitory response but instead tended to cause an increase in chemo¬ receptor discharge. Responses to the chemoreceptor stimulants sodium cyanide and hypoxia were potentiated following administration of dopamine-blocking agents. These results suggest the possibility that endogenous dopamine acts to depress afferent carotid chemoreceptor activity. Subsequent experiments in cats showed that the dopamine-uptake blockers benztropine and nomifensine, but not the monoamineoxidase inhibitor pargyline, potentiate the inhibitory action of injected dopamine and also potentiate chemoreceptor responses to sodium cyanide and hypoxia. These results imply that, in addition to its inhibitory action, endogenous dopamine has an excitatory action on chemoreceptor activity. It is suggested that the most likely physiological role for dopamine in the carotid body is as a chemical mediator in an 'amplification' system, modulating activity in sensory nerve endings which are themselves the chemoreceptors. Injection of acetylcholine in rabbits caused inhibition of afferent chemoreceptor activity, in contrast to the stimulation evoked in cats and dogs. In some experiments high doses of acetylcholine evoked a slight excitation which preceded the inhibition. This effect was probably brought about by an action on nicotinic receptors since it was blocked by mecamylamine but is unlikely to be of physiological significance. The muscarinic agonists methacholine and bethanechol, but not the nicotinic agonist subery1dicholine, also inhibited spontaneous chemoreceptor discharge indicating that the inhibition was brought about by an action on muscarinic receptors. The inhibition was blocked by atropine, although high doses were required to produce this effect. The inhibition is unlikely to be a consequence of a vascular action of acetylcholine since the vaso¬ dilator drugs sodium nitrite and sodium nitroprusside had little effect on chemoreceptor activity. The inhibition evoked by acetyl¬ choline was not reduced by a-f1upenthixol and is, therefore, unlikely to be secondary to dopamine release. It is proposed that acetylcholine may act as a transmitter in an inhibitory efferent pathway to the carotid body but is unlikely to act as an excitatory sensory transmitter.