The effect of cocaine and desipramine on neuronal uptake of [3H]-noradrenaline and sensitivity to noradrenaline of rat mesenteric resistance arteries.
1. The effects of cocaine and desipramine (DMI) on neuronal uptake (uptake1) of [3H]-noradrenaline (NA) and isometric tension development to exogenous NA were assessed in mesenteric resistance arteries of Wistar rats. 2. Both drugs concentration-dependently inhibited [3H]-NA uptake1, DMI being more potent than cocaine. The maximum inhibition produced by each drug was the same as that produced by denervation with 6-hydroxydopamine. In denervated vessels there was no effect of cocaine on [3H]-NA uptake1. 3. Cocaine, in the same concentration range which caused inhibition of uptake1, increased the sensitivity to NA, while DMI, in a concentration range which inhibited uptake1, did not increase the sensitivity to NA and at high concentrations reduced the sensitivity and maximal response to NA. Since DMI affected responses to NA but not responses to vasopressin and potassium its effect is probably related to blockade of alpha 1-adrenoceptors. 4. We conclude that the effect of cocaine on the sensitivity to NA reflects inhibition of uptake1 in rat resistance arteries, while DMI cannot be used to assess the functional effect of uptake1 in this preparation.
Byg
A M
AM
Department of Medicine, University of Manchester, UK.
Bund
S
S
Mulvany
M J
MJ
Aalkjaer
C
C
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003714:Denervation; D003891:Desipramine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000294:innervation; D009213:Myography; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D014667:Vasopressins; D012701:Serotonin; D016627:Oxidopamine; D003042:Cocaine; D011188:Potassium; D003891:Desipramine; D009638:Norepinephrine