Inhibitory action of dopamine on cat carotid chemoreceptors.

Abstract

The influence of some drugs which affect the dopaminergic system was studied on chemosensory responses to dopamine (DA), acetylcholine (ACh), sodium cyanide (NaCN) and hypoxia during experiments on pentobarbitone anesthetized cats in which chemoreceptor activity was recorded from the peripheral end of a sectioned sinus nerve. Spontaneous chemosensory activity was inhibited in a dose-dependent manner by DA (0.5-5 .mu.g, i.a. [intraarterial]). Higher doses (10-50 .mu.g) caused a delayed increase in discharge and were associated with inconsistent inhibitory responses. The DA antagonist .alpha.-flupenthixol (0.2 mg/kg, i.a.) blocked the inhibitory response to DA without affecting either the spontaneous discharge frequency or the response to ACh. The effect of NaCN was potentiated, and during hypoxia chemoreceptor activity increased more rapidly, although the maximum frequency attained was not appreciably different from control values. Similar results were obtained with haloperidol (0.5 and 1.0 mg/kg, i.v). Higher doses of .alpha.-flupenthixol (0.5-1.0 mg/kg, i.a.) increased spontaneous chemoreceptor activity, but this was regarded as a non-specific of the drug since at these doses the inhibitory effect of 5-hydroxytryptamine (5-HT) was also abolished. The animals were exposed to alternate periods of hypoxia and hyperoxia following administration of the tyrosine hydroxylase inhibitor .alpha.-methyl p-tyrosine (AMPT, 0.2-10 mg/kg, i.a.). The inhibitory response previously evoked by amphetamine was abolished, and EM studies showed a great reduction in the number of dense-cored granules, both of which suggested that DNA levels in the carotid body were substantially reduced. Responses to NaCN and hypoxia were slightly potentiated following AMPT, but neither spontaneous activity nor the response to ACh was affected. Apomorphine (0.05-0.2 mg/kg, i.a.) inhibited the chemoreceptor discharge for up to 45 min, an effect which was antagonized by .alpha.-flupenthixol (0.2 mg/kg, i.a.), implying it resulted from DA receptor stimulation. Although responses of NaCN, hypoxia and higher doses of ACh were reduced following administration of apomorphine, the reduction was not very marked. These results are not compatible with the Osborne and Butler theory, than in normoxia DA is tonically released in the carotid body and suppresses spontaneous chemosensory activity. Apparently DA modulates chemosensory activity by influencing the rate of increase in discharge, without affecting maximum discharge frequency. The mechanism whereby DA is released in response to increased chemosensory activity remains to be established.