| Summary: | Afferent chemoreceptor activity was recorded from the peripheral cut end of the carotid sinus nerve in pentobarbitone anaesthetized cats. The effects of purines, peptides and ouabain on chemosensory activity were studied. Purines. It was found that intracarotid injections of adenosine: AMP; ADP; ATP; CoA;Me-adenosine analogues: N6-methyladenosine, 2-chloroadenosine, 3'-deoxyudenosine but not 2'-deoxyadenosine; cyclic AMP; dibutyryl cyclic AMP increased spontaneous chemoreceptor discharge. The ATP analogues, a-5- methylene ATP decreased spontaneous chemoreceptor discharge, whereas the f-y-methylene ATP caused a slight increase in discharge. Adenine and the purine nucleosides inosine and guanosine had little or no effect on the discharge. The pyrimidine nucleosides cytidine and uridine were also studied and had little or no effect on spontaneous chemoreceptor discharge. Intracarotid injection of theophylline transiently depressed spontaneous chemosensory activity and potentiated the action of adenosine. Intracarotid injection of dipyridamole increased spontaneous chemoreceptor discharge and the chemoexcitation evoked by low doses of adenosine and ATP was potentiated whereas that caused by high doses was inhibited and associated with a decrease in arterial blood pressure. Dipyridamole administered intravenously increased the chemoexcitatory actions of both low and high doses of adenosine. Responses evoked by sodium cyanide were slightly and variably modified during an adenosine infusion and those evoked by acetylcholine and dopamine were increased. It is concluded that adenosine increases chemoreceptor activity by acting on an extracellularly located receptor, which is theophylline-insensitive and probably of the 11-site type. Peptides. The opioid peptides, methionine-enkephalin, leucine-enkephalin and ;-endorphin inhibited spontaneous chemoreceptor discharge. 5-endorphin was a less potent inhibitor and the inhibition it evoked was very similar to that of morphine. Chemoinhibition induced by 5-endorphin was greatly reduced by naloxone; the inhibition associated with the enkephalins was also decreased, although not so markedly. Vasoactive intestinal polypeptide in low doses decreased spontaneous chemoreceptor activity whereas higher doses of the same substance increased chemoreceptor activity as did cholecystokinin octapeptide. Substance P was unable to overcome the chemoinhibitory effect of methionine-enkephalin. It is concluded that peptides such as methionine-enkephalin, leucine-enkephalin and vasoactive intestinal polypeptide, known to be present in the carotid body as well as others present in the brain, such as 5-endorphin and cholecystokinin octapeptide, influence carotid body chemoreceptor activity. The opioid peptides act via naloxone-sensitive receptors. Ouabain. Ouabain increased spontaneous chemoreceptor activity. During infusions the excitation was followed by a decline in discharge to frequencies near the control level. During the excitation the stimulatory action of sodium cyanide, carbon dioxide-equilibrated Locke solution and acetylcholine were potentiated. as was the chemoinhibition induced by dopamine. During the post-excitatory phase the responses evoked by these substances were reduced or abolished. It appears that ouabain has two distinct actions on the carotid body chemosensory activity: a 'sensitizing' followed by a 'desensitizing' phase. The possibility that the various substances investigated act via a common mechanism (e.g. adenylate cyclase-cyclic AMP system) is discussed.
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