L-DOPA and high oxygen influence release of catecholamines from the cat carotid body

Current modelling of carotid body (CB) chemotransduction postulates an essential role for neurotransmitters, including dopamine (DA). Catecholamines (CA) released from incubated/superfused cat CBs has often been reported to diminish rapidly over the course of the exposure. The purpose of the first set of experiments was to determine the effects of including L-dihydroxyphenylalanine (L-DOPA), the immediate precursor to DA, in the incubation medium. CBs were removed from deeply anesthetized cats, cleaned of connective tissue, and placed in separate incubation tubes containing Krebs Ringer Bicarbonate solution (KRB) at 37°C. One tube contained 40 μ M L-DOPA. Both tubes were bubbled for 2 hr with a normoxic gas mixture (21%O₂/6%CO₂). This was followed immediately by a 30-minute exposure to a hypoxic gas mixture (4% O₂/5% CO₂). The mean amounts of DA, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and norepinephrine (NE) released during 30 min exposures were always greater when L-DOPA was present. The use of gas mixture like the above normoxic gas mixture in incubation studies has often been considered quasi-hypoxic. Hence, in a second set of experiments we tested the effect of high oxygen mixture (95% O₂/5% CO₂). All other features of these experiments were the same as the above. The high oxygen environment correlated with lower DA release suggesting a reduced excitation/inhibition. The subsequent exposure to hypoxia, however, provoked a much larger release of DA and NE. The data demonstrate the substantial effect of oxygen on the release of CAs and the apparent need of a DA precursor like L-DOPA to allow detection of the changes in CA release from the CBs upon exposure to a hypoxic stimulus.