Acute epinephrine treatment fails to facilitate stimulus-induced neurotransmitter overflow in the isolated perfused rat kidney.
The effects of acute in vitro epinephrine treatment (40 nM, 1 hr) on stimulus-induced neurotransmitter overflow from the isolated perfused kidney were examined. This treatment resulted in the release of both norepinephrine and epinephrine upon nerve stimulation but no increase in fractional stimulus-induced overflow. Experiments utilizing beta and/or alpha adrenoceptor blockade revealed that beta adrenoreceptor blockade alone had no effect on overflow but that a dose-dependent decrease in stimulus-induced overflow was produced by beta adrenoceptor blockade after alpha adrenoceptor blockade. Thus, under normal conditions the facilitatory influence of epinephrine via prejunctional beta adrenoceptors is masked by the prejunctional alpha adrenoceptor negative feedback loop. The effects of extraneuronal presentation of isoproterenol, salbutamol and epinephrine on stimulus-induced neurotransmitter overflow also were examined. In the absence of alpha adrenoceptor blockade, only epinephrine failed to enhance neurotransmitter overflow. After competitive alpha adrenoceptor blockade, all three agents produced significant increases in stimulus-induced neurotransmitter overflow from the rat kidney, although alpha adrenoceptor stimulation appeared to limit this effect at high agonist concentrations. We conclude that the dominance of prejunctional alpha adrenoceptors in the rat kidney results in the inability of epinephrine to produce beta adrenoceptor-mediated facilitation of neurotransmitter overflow even when it is incorporated into renal neurotransmitter stores and coreleased with endogenous norepinephrine upon nerve stimulation.
Schwartz
D D
DD
Department of Pharmacology, College of Pharmacy, University of Houston, Texas.
Eikenburg
D C
DC
D000818:Animals; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000502:physiology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010477:Perfusion; D010646:Phentolamine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology
D018377:Neurotransmitter Agents; D011412:Propanolamines; D011941:Receptors, Adrenergic; C026777:ICI 118551; D007545:Isoproterenol; D004837:Epinephrine; D010646:Phentolamine