Abstract
On guinea pig aortic anphenous vein strips, cumulative and non-cumulative dose-response curves were determined for noradrenaline and isoprenaline. Cumulative dose-response curves for noradrenaline were significantly flatter than non-cumulative curves. However, for isoprenaline cumulative and non-cumulative dose-response curves were identical, and their slopes corresponded to that of the non-cumulative dose-response curve for noradrenaline. After pretreatment with cocaine plus iproniazid plus tropolone, cumulative dose-response curves for noradrenaline were as steep as non-cumulative curves. Experiments with the oil immersion technique showed that isoprenaline was much more slowly inactivated than noradrenaline. There are two possible explanations for the observed changes in slopes of dose-response curves: (a) during cumulative dose-response curves more of the noradrenaline can be inactivated by the tissue (if the agonist is inactivated at a high rate) than during non-cumulative dose-response curves; (b) during cumulative dose-response curves desentization develops to nonadrenaline in the absence but not in the presence of cocaine plus iproniazid plus tropolone; however, desentization does not develop to isoprenaline.
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