Effect of desipramine on the effects of alpha-adrenoceptor inhibitors on pressor responses and release of norepinephrine into plasma of pithed rats.
The role of neuronal uptake inhibition on the efficiency of alpha 1- and alpha 2-antagonists in inhibiting pressor responses and the release of plasma catecholamines in pithed rats were studied. Prazosin, in doses which selectively blocked alpha 1-adrenoceptors (0.01-0.1 mg/kg), was more effective than yohimbine, a relatively selective alpha 2-antagonist, in inhibiting stimulation-induced pressor responses. Yohimbine (0.1-1 mg/kg) potentiated or did not alter the pressor responses to stimulation, whereas it blocked pressor responses to administered norepinephrine (NE) more effectively than did prazosin. Inhibition of uptake by desipramine (DMI), 0.3 mg/kg, did not affect prazosin inhibition of stimulation-induced pressor responses though it increased NE overflow into circulation. In yohimbine-treated rats, DMI potentiated significantly (p less than 0.001) both pressor and NE responses to stimulation. DMI partially reversed prazosin inhibition of pressor response to administered NE (p less than 0.001) and potentiated the response in yohimbine-treated rats (p less than 0.01). The results are consistent with the view that endogenously released NE acts at intrajunctional alpha 1-adrenoceptors, whereas exogenous NE acts predominantly at extrajunctional alpha 2-adrenoceptors. The neuronal uptake site appears to be functionally (and perhaps anatomically) located outside the synaptic cleft, between intrajunctional alpha 1-postsynaptic receptors and extrajunctional alpha 2-adrenoceptors.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003655:Decerebrate State; D003891:Desipramine / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin