Carotid body dopamine content and release by short term hypoxia: Effect of haloperidol and alpha methyl paratyrosine

Dopamine (DA) is thought to modulate the transduction of the hypoxic stimulus by the glomus cell in the carotid body (CB). The hypothesis tested here is that presynaptic DA D2 receptors (D2's) located on the type I cell function as autoreceptors to control DA release and/or synthesis. The aim of the study was to compare the effects of blocking D2's with haloperidol and DA synthesis with alpha methyl paratyrosine (AMPT) on the in vitro carotid body DA response to hypoxia. 54 CB's sampled from adult rabbits were incubated for one hour in a surviving medium bubbled with either 100% O-2 or 8% O-2. Sixteen CB's served as control (100% O-2:n=8, 8% O-2: n=8), 18 (100% O-2: n=8) 8% O-2: n=10) were sampled from rabbits pretreated with AMPT and 20 (100% O-2: n=12, 8% O-2: n=8) were incubated with micromolar concentrations of haloperidol. Al the end of exposure, DA contained in the carotid body (DA(CB)) and released in the surviving medium (DA(r)) were measured by HPLC. In 100% O-2, DA(CB) was not different between either AMPT or haloperidol and control, but DA(r) was significantly higher in the haloperidol group compared with control(mean +/- SE: 26.6 +/- 7.4 versus 7.6 +/- 2.0 pmol/h, P < 0.02). In 8% O-2) control DA(CB) (576 +/- 133 pmol/CB) was significantly higher than AMPT or haloperidol (respectively 228 +/- 29.6 and 246 +/- 49.9 pmol/CB, P < 0.01) and control DA(r) (234 +/- 72.3 pmol/h) was also significantly higher than AMPT or haloperidol (respectively 28.8 +/- 5.2 and 40.6 +/- 11.4 pmol/h, P < 0.01). Finally, DA(r) was significantly larger in 8% O-2 than in 100% O-2 in control and AMPT groups (P < 0.01), but not in the haloperidol group. The increase in DA(r) by haloperidol in the resting CB is consistent with the blockade of D2's regulating DA release. The decreased DA(r) in 8% O-2 after AMPT suggests that increased DA synthesis contributes to maintain DA secretion by the type I cell exposed to short term hypoxia. The lack of difference in DA(r) between 8% O-2 and 100% O-2 after haloperidol probably reflects non specific - i.e., D2 independent - effect of micromolar concentration of haloperidol on DA synthesis and/or sodium-calcium exchangers during hypoxia.