Epinephrine and prejunctional adrenoceptor modulation of neurotransmission in the rat kidney

The aim of this study was to investigate the influence of epinephrine on the modulation of stimulus-induced neurotransmitter overflow by prejunctional adrenoceptors in the isolated perfused rat kidney. In this study, chronic experiments consisted of epinephrine (lOOmcg/kg/hr s.c.) or vehicle administration for six days. In acute studies, isolated kidneys were perfused with epinephrine (40nM) for one hour. Chronic and acute epinephrine treatment resulted in the incorporation of epinephrine into neuronal stores and the co-release of epinephrine with norepinephrine during stimulation. Only norepinephrine was detected in the perfusate and kidneys of vehicle-treated rats. Chronic, but not acute, epinephrine treatment resulted in an enhanced stimulus-induced fractional overflow. The modulation of neurotransmitter overflow by prejunctional adrenoceptors was examined using adrenoceptor antagonists. No beta-adrenoceptor-mediated facilitation of neurotransmitter overflow was observed following either chronic or acute epinephrine treatment unless prejunctional alpha-adrenoceptors were blocked. Examination of the influence of prejunctional alpha-adrenoceptors following betaadrenoceptor blockade revealed a reduced ability of prejunctional alpha-adrenoceptors to modulate stimulus-induced neurotransmitter overflow following chronic epinephrine administration. Furthermore, the intrinsic efficacy of epinephrine to enhance overflow via prejunctional beta-adrenoceptors was significantly less than isoproterenol suggesting the partial agonistic actions of epinephrine at these receptors. Therefore, the enhanced fractional overflow following chronic epinephrine administration was due to a compromised prejunctional alpha-adrenoceptor influence on neurotransmitter overflow, and not due to beta-adrenoceptor-mediated facilitation of neurotransmitter overflow. A beta-adrenoceptor-mediated facilitation of neurotransmitter Overflowwas only demonstrated following alpha-adrenoceptor blockade and only when epinephrine is present. The proposed partial agonistic actions of epinephrine at prejunctional beta-adrenoceptors and the dominance of the prejunctional alpha-adrenoceptor-mediated negative feedback loop may account for the lack of a beta-adrenoceptor-mediated facilitation of sympathetic neurotransmission in the rat kidney by epinephrine.