Adenosine receptor antagonism attenuates angiotensin II effects on adrenergic neurotransmission in the rabbit isolated vas deferens.
Angiotensin II augments adrenergic neurotransmission in the rabbit isolated vas deferens and suppresses purinergic neurotransmission. This study tests the hypothesis that angiotensin II augments adrenergic neurotransmission by depressing the neuronal release of ATP, resulting in suppressed formation of the inhibitory neuromodulator, adenosine or a related purine. Exogenous ATP added to the vasa deferentia increased adenosine formation and depressed adrenergic neurotransmission thus providing indirect support for the hypothesis. The adenosine receptor antagonist, 8-(sulfophenyl)theophylline (10 and 100 microM) depressed responses to exogenous adenosine and ATP but did not alter contractile responses to nerve stimulation or exogenously administered norepinephrine thus indicating that endogenous adenosine had no basal influence upon neurotransmission. However, the 8-(sulfophenyl)theophylline reduced angiotensin II effects on both adrenergic neurogenic contractions and evoked norepinephrine release. Additionally, the augmentation of adrenergic neurogenic contractions by angiotensin II was enhanced in the presence of ATP. These results are consistent with an ATP involvement in angiotensin effects on adrenergic neurotransmission and contrary to the initial hypothesis, suggest that purines enhance adrenergic neurotransmission in the presence of angiotensin II.
Trachte
G J
GJ
Department of Pharmacology, University of Minnesota, Duluth School of Medicine, Duluth.
Heller
L J
LJ
D000241:Adenosine / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D058914:Purinergic Antagonists; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011983:Receptors, Purinergic / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism
D058914:Purinergic Antagonists; D011941:Receptors, Adrenergic; D011983:Receptors, Purinergic; D000804:Angiotensin II; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D000241:Adenosine; D009638:Norepinephrine