title: Possible involvement of presynaptic alpha 1-adrenoceptors in the effects of idazoxan and prazosin on 3H-noradrenaline release from tail arteries of SHR.
abstract: The effects of several alpha-adrenoceptor antagonists have been examined on tritium release elicited by electrical stimulation from isolated perfused SHR tail artery preparations prelabelled with 3H-noradrenaline (3H-NA). Phentolamine and yohimbine potently facilitated the stimulation evoked release of tritium at low frequencies of stimulation, but the alpha 2-adrenoceptor antagonist idazoxan was only weakly active at 1 mumol/l, despite antagonising the clonidine-evoked inhibition of 3H-release at a lower concentration of 0.1 mumol/l. The alpha 1-adrenoceptor antagonists prazosin and corynanthine also increased stimulation evoked tritium release in this preparation, suggesting the presence of prejunctional alpha 1-adrenoceptors. Furthermore, the alpha 1-adrenoceptor agonist methoxamine (3 mumol/l) caused a significant inhibition of tritium-evoked release, an effect which was blocked by prazosin (10 nmol/l). When alpha 1-adrenoceptors were blocked in the presence of prazosin, idazoxan (0.1 mumol/l) produced a significant facilitatory effect on the electrically-evoked release of 3H-transmitter. On the other hand, when alpha 2-adrenoceptors were blocked in the presence of yohimbine, exposure to idazoxan (0.1 mumol/l) reduced significantly the stimulation-evoked release of tritium elicited by electrical stimulation. The results indicate that in the SHR tail arteries, idazoxan has a partial agonist inhibitory activity on transmitter release, which can mask the facilitatory effects due to blockade of presynaptic alpha 2-adrenoceptors. The inhibitory effects of idazoxan appear to involve presynaptic alpha 1-adrenoceptors, which when stimulated, reduce 3H-NA release in SHR tail arteries.
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology*; D004147:Dioxins / Q000494:pharmacology*; D004558:Electric Stimulation; D019329:Idazoxan; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004147:Dioxins; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin; D019329:Idazoxan