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  • Title: The recovery of alpha-adrenoceptor function and binding sites after phenoxybenzamine. An index of receptor turnover?
    Author: Hamilton CA, Dalrymple HW, Reid JL, Sumner DJ.
    Journal: Naunyn Schmiedebergs Arch Pharmacol; 1984 Jan; 325(1):34-41. PubMed ID: 6324006.
    Abstract:
    The recovery of peripheral alpha-adrenoceptor function and binding sites was studied in male New Zealand white rabbits after treatment with the irreversible adrenoceptor antagonist phenoxybenzamine. Phenoxybenzamine (5 mg/kg) was administered intravenously and the animals studied 30 min to 12 days later. Pressor dose response curves to intravenous phenylephrine, noradrenaline and guanabenz were constructed in vivo in conscious animals. The contractile response of abdominal aorta and renal artery to phenylephrine and noradrenaline was examined in vitro and the recovery of specific prazosin and clonidine binding to spleen membranes investigated in radioligand binding studies. The half life (t 1/2) for recovery of maximum pressor response in vivo ranged from 0.9 +/- 0.2 days for phenylephrine to 1.4 +/- 0.1 days for guanabenz. The t 1/2 for recovery of ED50 was not significantly different to t 1/2 for recovery of maximum pressor response and ranged from 0.8 +/- 0.2 days for noradrenaline to 1.3 +/- 0.3 days for phenylephrine. Half life for recovery of maximum response and EC50 in the isolated tissues was similar to that obtained in vivo for recovery of pressor responses and ranged from 0.4 +/- 0.1 days for the EC50 of noradrenaline in the renal artery to 1.2 +/- 0.6 days for maximum response to phenylephrine in the abdominal aorta. The rate of recovery of specific clonidine binding did not differ significantly from the rate of recovery of pressor responses to the alpha 2-selective agonist guanabenz. t 1/2 for maximum number of specific clonidine binding sites, Bmax was 1.6 +/- 0.9 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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