Pharmacological characterization of the receptor involved in chemoexcitation induced by adenosine

Experiments were performed on cats anaesthetized with pentobarbitone in which carotid body chemoreceptor activity was recorded from the peripheral end of a sectioned carotid nerve. Intracarotid (i.c.) injections of adenosine and its analogues, NECA (5'-N-ethylcarboxamidoadenosine), L-PIA(L-N6-phenylisopropyladenosine), and D-PIA(D-N6-phenylisopropyladenosine), caused dose-related increases in chemosensory discharge. The rank order of potency as chemoreceptor stimulants was: NECA greater than adenosine greater than L-PIA greater than D-PIA. Infusion of theophylline antagonized the chemoexcitatory effects of NECA, and infusion of 8-phenyltheophylline (8-PT), which is a more potent adenosine antagonist with less activity as a phosphodiesterase inhibitor, reduced the chemoexcitation induced by adenosine. Infusion of 8-PT (10 micrograms min-1 i.c.), a dose which substantially reduced the effect of injected adenosine, also reduced the sensitivity of carotid chemoreceptors to hypoxia (10% O2 for 4 min). It is concluded that the adenosine receptors in the cat carotid body which mediate chemosensory excitation are xanthine-sensitive and appear to be of the A2 sub-type. Adenosine, released within the carotid body by physiological stimuli, may be involved in chemoexcitation.