Concomitant Effect of Acetylcholine and Dopamine on Carotid Chemosensory Activity in Catecholamine Depleted Cats

Abstract

Carotid body chemotransduction mechanisms involve many neurotransmitters that are synthetized, stored, and released from the chemoreceptor cell. Acetylcholine (ACh) and dopamine (DA) are the main transmitters studied to date. It has been suggested that, at least in cats, ACh is an excitatory whereas DA is an inhibitory transmitter in the carotid body (as review see Eyzaguirre and Zapata, 1884; Fidone et al., 1997; Fitzgerald, 2000). However, their role on chemosensory activity in response to hypoxia is still debated. Recently, in catecholamine-depleted cats where the storage and release of carotid body DA was greatly impeded by the use of ∝-methyl-paratyrosine and reserpine (Bairam and Marchai, in press), DA infiision was showed to inhibit the carotid sinus nerve chemosensory discharge rate (CSND) while ACh reversed the effect under basal condition. In response to hypoxia, DA slowed the initial increase of CSND whereas ACh accelerated it, while neither drug altered the steady-state chemosensory discharge under hypoxic conditions. One interpretation of these results was that DA infusion prevented the expression of ACh excitatory effect during hypoxia as it was infused methyl-paratyrosine maintained throughout ACh administration. Using a similar model of adult cats pre-treated with oc-methyl-paratyrosine and reserpine (Bairam and Marchai, in press), we investigated the effect of 1) ACh infusion on CSND response to different inspiratory oxygen concentrations (Fi0₂) and 2) DA infusion while ACh is maintained. This protocol of drug administration should reveal the excitatory role of ACh on CSND under basal condition particularly in hypoxia. Indeed, the methyl-paratyrosine with oc-methyl-paratyrosine and reserpine, which inhibits and depletes catecholamine synthesis and storage (Leitner and Roumy, 1986; Fitzgerald et al., 1983), should minimize the effects of endogenous release of DA on CSND.