Influence of desipramine on the uptake and efflux of radiolabelled bretylium and bethanidine in the adventitial and media-intimal layers of rabbit aortic strips.
The desipramine-sensitive uptake (neuronal uptake) of 14C-bretylium and 14C-bethanidine into the rabbit aortic adventitial layer from 3 X 10(-6) M solutions increased with time during a 20 min incubation. For both compounds a neuronal uptake of 50 pmol/50 mg wet weight adventitia was associated with 10% block of the contractile response to field stimulation at 16 Hz and 150 pmol/50 mg with 60% block. The concentration of blocking agents inside the neuron at 50% blockade was calculated to be 260 X 10(-6) M, an 87-fold increase over the medium. The bretylium in the neuron decreased by 50% during 20 min washout, and bethanidine by 29%. Desipramine when added to the bath 20 min following the addition of the blocking agents led to a loss of bretylium but not of bethanidine from the adventitia. Desipramine had little or no effect on the uptake, washout or disposition of either blocking agent in the media-intimal layers. The data indicate that bretylium has a greater propensity than bethanidine to be lost from the neurons; however, it appears to be recycled back through the membrane via the amine pump more readily than bethanidine. The fact that conservative calculations indicate that the neuronal membrane slowly established a concentration of the blocking agents within the neuron that is known to produce rapid local anesthesia when topically applied to adrenergic nerve trunks and which approaches a concentration needed to inhibit sensory endings suggests that local anesthesia may play a role in the mechanism of neuron blockade.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D001627:Bethanidine / Q000378:metabolism*; D001949:Bretylium Compounds / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006146:Guanidines / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009474:Neurons / Q000378:metabolism*; D011817:Rabbits
D001949:Bretylium Compounds; D006146:Guanidines; D003891:Desipramine; D001627:Bethanidine