Modulation of noradrenaline release from cat cerebral arteries by presynaptic alpha 2-adrenoceptors. Effect of chronic treatment with desipramine and cocaine.
1. Field electrical stimulation elicited an increase of the tritium efflux over the basal level from cat cerebral arteries previously incubated with (+/-) [3H]noradrenaline ([3H]NA). 2. This efflux was: (a) reduced by clonidine, NA or B-HT 920; (b) unaffected by methoxamine, prazosin and yohimbine (10(-6) M); (c) reduced by yohimbine (5 x 10(-6) M), and (d) increased by phentolamine. 3. The effect of clonidine was blocked by yohimbine. 4. The daily treatment with the neuronal uptake blockers desipramine (10 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.) [during 12 days], antagonized the inhibitory action of clonidine totally or partially, respectively. 5. These results suggest: (1) the existence of presynaptic alpha 2-adrenoceptors in these arteries, which modulate the NA release, and (2) that chronic treatment with desipramine or cocaine induces a subsensitivity of these alpha 2-receptors, which facilitates the NA release.
Balfagón
G
G
Departamento de Farmacología, Terapéutica y Fisiología, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Marín
J
J
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D013779:Tetrodotoxin; C024763:talipexole; D003042:Cocaine; D003000:Clonidine; D003891:Desipramine; D009638:Norepinephrine