Evidence for the involvement of alpha 1-adrenoceptors in negative feedback regulation of noradrenergic transmitter release in rat atria.
Experiments were undertaken to determine if prejunctional alpha 1-adrenoceptors are involved in autoinhibitory regulation of transmitter noradrenaline release in rat atria. The noradrenergic transmitter stores in rat isolated atria were radiolabelled with [3H]noradrenaline and transmitter release was deduced from the efflux of the radiolabel evoked by field stimulation of the atrial intramural sympathetic nerves. Phentolamine (3 mumol/l) and prazosin (0.1 and 3 mumol/l) enhanced the release of radiolabel evoked by stimulation with trains of 4, 8 and 16 pulses, whereas idazoxan (10 mumol/l) enhanced release evoked by stimulation with 8 and 16 pulses. Idazoxan and prazosin were about equi-effective in enhancing the evoked release but phentolamine produced much greater enhancement than either idazoxan or prazosin. Combination of idazoxan (10 mumol/l) and prazosin enhanced the stimulation-evoked release with 4, 8 and 16 pulses to the same extent as phentolamine (3 mumol/l). The selective alpha 1-adrenoceptor agonist methoxamine (10 mumol/l) inhibited stimulation-evoked release and this effect was blocked by the alpha 1-adrenoceptor antagonist prazosin (0.1 mumol/l). The findings indicate that alpha 1-adrenoceptors may contribute to autoinhibitory feedback regulation of transmitter release in rat atria.
Story
D F
DF
Standford-Starr
C A
CA
Rand
M J
MJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology; D004558:Electric Stimulation; D005246:Feedback; D005260:Female; D006325:Heart Atria; D019329:Idazoxan; D008729:Methoxamine / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D009435:Synaptic Transmission
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D008729:Methoxamine; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan; D010646:Phentolamine