Effects of the novel dopamine DA2-receptor agonist carmoxirole (EMD 45609) on noradrenergic and purinergic neurotransmission in rat isolated kidney.

The effects of the classical dopamine DA2-receptor agonist quinpirole (LY 171555) and the recently characterized DA2-receptor agonist, carmoxirole (EMD 45609), on neurotransmission in rat isolated kidney were investigated. After preincubation with 3H-noradrenaline, the renal nerves were electrically stimulated. The stimulation induced (S-I) outflow of radioactivity was taken as an index of noradrenaline release. Quinpirole (0.3 mumol/l) inhibited S-I outflow of radioactivity and pressor-responses to renal nerve stimulation (RNS) at 1 Hz. Both effects of quinpirole were blocked by the DA2-receptor antagonist S(-)-sulpiride (10 mumol/l). The alpha 1, alpha 2-adrenoceptor antagonist phentolamine (1 mumol/l) did not block the inhibitory effect of quinpirole. Carmoxirole (0.003 and 0.03 mumol/l) did not alter and carmoxirole (0.3 mumol/l) even enhanced S-I outflow of radioactivity, however, pressor responses to RNS were markedly reduced by carmoxirole (0.003-0.3 mumol/l). Pressor responses to RNS were also markedly reduced by the alpha 1-adrenoceptor antagonist prazosin (0.1 mumol/l). Carmoxirole (0.3 mumol/l), prazosin (0.1 mumol/l) and phentolamine (1 mumol/l) totally abolished pressor responses to exogenous noradrenaline (0.05 mumol/l). In contrast, quinpirole (0.3 mumol/l) did not alter pressor responses to exogenous noradrenaline (0.05 mumol/l). Furthermore, carmoxirole (0.003-0.3 mumol/l) markedly reduced pressor responses induced by the alpha 1-adrenoceptor agonist methoxamine (1 mumol/l) but even the highest concentration of carmoxirole (0.3 mumol/l) had no effect on pressor responses induced by bolus injections of either neuropeptide Y (1.5 ng) or angiotensin II (1 ng). Phentolamine (1 mumol/l) by itself markedly enhanced S-I outflow of radioactivity and pressor responses to RNS were virtually unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)