Modulation of noradrenergic transmission in the rat isolated portal vein: role of prejunctional alpha 2-adrenoceptors and beta-adrenoceptors.
1. The effect of several adrenoceptor agonists and antagonists on the spontaneous and stimulus-evoked release of [3H]noradrenaline was studied in rat isolated portal vein. 2. Yohimbine (10(-6)M) increased the stimulus-evoked [3H]noradrenaline efflux. Adrenaline alone (3 x 10(-6)M) was without effect, while it increased the resting efflux when added together with yohimbine. 3. Propranolol alone was without effect on the release of [3H]noradrenaline. When added (2 x 10(-6)M) at the same time as yohimbine, it reduced the stimulation-induced 3H efflux. When added before adrenaline and yohimbine, propranolol (10(-5)M) reduced both spontaneous and stimulus-evoked release of [3H]noradrenaline. 4. The effect of several beta-blocking drugs was measured on the enhancing effect of yohimbine on the stimulation-evoked 3H efflux. The beta 1-adrenoceptor blocking drugs: atenolol (5 x 10(-6) and 10(-5) M), metoprolol (5 x 10(-6) and 10(-5) M), like the more selective bisoprolol (2 x 10(-6) and 4 x 10(-6) M) inhibited yohimbine activity. Likewise, propranolol (2 x 10(-6) and 5 x 10(-6)M) and the beta 2-adrenoceptor blocker ICI 118551 exhibited an antagonistic effect. 5. These results indicate the possibility for noradrenaline to activate presynaptic beta-adrenoceptors in rat portal vein. They show an interaction between the presynpatic alpha 2- and beta-adrenoceptor mediated systems in the release of noradrenaline. They suggest the presence and the activity of facilitatory beta 1-adrenoceptors.
Laboratorio de Farmacognosia y Farmacodinamia, Facultad de Farmacia, Salamanca, Spain.
A V
AV
Ortiz de Urbina
M
M
Davy
M
M
Midol-Monnet
M
M
Heimburger
F
F
Beslot
Y
Y
Cohen
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009638:Norepinephrine / Q000502:physiology*; D011169:Portal Vein / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine