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 s timulus by the glomus cell in the carotid body (CB). The hypothesis te sted here is that presynaptic DA D2 receptors (D2's) located on the ty pe I cell function as autoreceptors to control DA release and/or synth esis. The aim of the study was to compare the effects of blocking D2's with haloperidol and DA synthesis with alpha methyl paratyrosine (AMP T) on the in vitro carotid body DA response to hypoxia. 54 CB's sample d 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 contro l (100% O-2:n=8, 8% O-2: n=8), 18 (100% O-2: n=8) 8% O-2: n=10) were s ampled 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 pmo l/h, P < 0.02). In 8% O-2) control DA(CB) (576 +/- 133 pmol/CB) was si gnificantly 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 p mol/h) was also significantly higher than AMPT or haloperidol (respect ively 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 AM PT groups (P < 0.01), but not in the haloperidol group. The increase i n DA(r) by haloperidol in the resting CB is consistent with the blocka de 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 s ecretion 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 pro bably reflects non specific - i.e., D2 independent - effect of micromo lar concentration of haloperidol on DA synthesis and/or sodium-calcium exchangers during hypoxia.