Effect of desipramine on propranolol-induced diminution of noradrenaline release by nerve stimulation.
In atria from rats killed 1 h after either chronic parenteral (daily subcutaneous injections of 5 mg/kg/day for 15 days) or prolonged oral administration of (-)-propranolol (1 mg/ml ad libitum during 15 days) there was a 50% decrease in the overflow of [3H]noradrenaline ([3H]NA) elicited by cardioaccelerans nerve stimulation at 2 Hz, as previously reported for the in vitro exposure of guinea pig atria to propranolol. The chronotropic responses to nerve stimulation and to isoprenaline were also significantly reduced. On the other hand, 40 h after the last injection of propranolol, the overflow of [3H]NA induced by stimulation was still reduced to 50% of the control values, whereas no blockage to nerve stimulation or to isoprenaline was observed. Neither the basal output of [3H]NA nor the tissue levels of the endogenous transmitter were modified by any of the treatment schedules applied. In a separate set of experiments performed in isolated guinea pig atria stimulated at 4 Hz during 1 min, the in vitro exposure to 0.5 microM desipramine prevented the 30% decrease in the overflow of [3H]NA caused by 0.1 microM (-)-propranolol. Desipramine, by itself, did not modify the overflow of the transmitter. It is concluded that propranolol, both in vitro and after chronic in vivo treatments, reduces the overflow of [3H]NA in response to nerve stimulation. The fact that the in vitro effect of the beta-blocker is antagonized by desipramine suggests that propranolol may have to be taken up by the nerve terminals in order to exert its presynaptic inhibition on the release of noradrenaline.
D000319:Adrenergic beta-Antagonists / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003891:Desipramine / Q000494:pharmacology*; D004285:Dogs; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D011433:Propranolol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D003891:Desipramine; D009638:Norepinephrine