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Inhibition of norepinephrine uptake by phenoxybenzamine and desmethylimipramine in the isolated guinea-pig atrium

P Sanchez-Garcia, AG Garcia, R Martinez-Sierra and A Velasco-Martin

The effects of phenoxybenzamine (PBZ) and desmethylimipramine (DMI) on 3H-norepinephrine uptake by sympathetic nerve terminals of isolated guinea-pig left atrium has been investigated in the absence and in the presence of norepinephrine, tyramine, cocaine and isoproterenol, used as protecting agents. PBZ blocked the uptake of 3H-norepinephrine by 50% at a concentration of 3 micronM. For DMI the ID50 was approximately 0.33 micronM. These doses were used for all subsequent protection experiments. When incubation with PBZ was carried out in the presence of tyramine (574 micronM) the blocking effects of PBZ were completely reversed. In contrast, tyramine was unable to protect against 3H- norepinephrine uptake blockade elicited by DMI. Norepinephrine (20 micronM) or cocaine (29 micronM) afforded no protection against DMI- induced 3H-norepinephrine uptake blockade, but both agents significantly protected against blockade of PBZ. Isoproterenol (40 micronM) was unable to protect against 3H-norepinephrine uptake blockade evoked either by PBZ or DMI. The results provide strong evidence for a different site and/or mechanism of action of PBZ and DMI on the norepinephrine uptake system at adrenergic nerve terminals.

Volume 201, Issue 1, pp. 192-198, 04/01/1977
Copyright © 1977 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics.