Evidence that there are subcellular pools of norepinephrine and that there is flux of norepinephrine between these pools.
d-Amphetamine evokes blood pressure responses that are dose-dependent in magnitude and in shape. At a high dose, d-amphetamine evokes a response that decays biphasically. Response decay is not due to receptor desensitization or to decreasing plasma levels of drug. The first component of the biphasic decay (early, transient response) has an apparent peak of approximately 56 mm Hg and a rate constant for decay of approximately 0.043-min-1. The second component (late, relatively stable response) has an apparent peak of approximately 27 mm Hg and a rate constant for decay less than 0.0043-min-1. Chronic reserpine treatment diminishes the blood pressure response to a high dose of d-amphetamine, but it exerts a differential effect on the two components of the response. The ID50 for reducing the early, transient response is greater than 800 micrograms/kg; the ID50 for reducing the late, relatively stable response is approximately 100 micrograms/kg. Acute reserpine treatment enhances blood pressure responses to d-amphetamine, mainly by enhancing the early, transient response. In addition, acutely administered reserpine reverses the tachyphylactic effect of d-amphetamine. The data are used to construct a model for norepinephrine storage in postganglionic sympathetic nerves and to propose a model for d-amphetamine-induced tachyphylaxis.
D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003913:Dextroamphetamine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology; D008954:Models, Biological; D009411:Nerve Endings / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D012110:Reserpine / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism*; D013618:Tachyphylaxis
D006892:Hydroxydopamines; D008781:Methyltyrosines; D012110:Reserpine; D003913:Dextroamphetamine; D009638:Norepinephrine