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- W2006251277 abstract "Uptake and displacement of three adrenergic receptor ligands, [3H]dihydroalprenolol ([3H]DHA), [3H]epinephrine ([3H]EPI) and [3H]clonidine ([3H]CLON), were examined in isolated rabbit lungs by recirculating perfusion. Removal of [3H]DHA was the most extensive (85% uptake; 6.6 ml/min clearance), [3H]CLON removal was intermediate (50%; 3.8 ml/min), and [3H]EPI removal was the lowest (33%; 1.2 ml/min). Specific displacement of each radioligand from lung was attempted using several competing agents. Both (--)- and (+)-propranolol equally displaced [3H]DHA from lung. Phentolamine, (--)-phenylephrine and (--)-epinephrine were unable to displace 10 nM [3H]EPI from lung, although the latter two agents did produce concentration-dependent increases in perfusion pressure. High concentrations of (--)-epinephrine, which produced near maximal physiological responses, inconsistently displaced 30-4- nM [3H]EPI from lung. [3H]Clonidine was displaced by unlabeled clonidine at concentrations that caused increases in perfusion pressure. Pretreatment of lungs with either 10 microM phentolamine or phenoxybenzamine did not alter the total amount of [3H]CLON displaced by clonidine, suggesting that [3H]CLON was displaced predominantly from non-specific sites, perhaps preventing detection of [3H]CLON displacement from specific (receptor) sites. Alternatively, these results may be interpreted as inhibition of uptake of each radioligand. Thus, both (--)- and (+)-propranolol interfered with [3H]DHA removal, suggesting a common mechanism for uptake and/or retention for these two beta-adrenergic receptor antagonists. Inhibition of [3H]EPI removal was observed only at high concentrations of (--)-epinephrine which indicates that pulmonary removal of epinephrine occurs through a low affinity uptake system. [3H]Clonidine removal was effectively inhibited by the same (microM) concentrations of unlabeled clonidine that produced physiological responses. Neither phentolamine nor phenoxybenzamine was able to interfere with pulmonary removal of [3H]CLON. Therefore, uptake and displacement of these adrenergic receptor radioligands showed no correlation with pharmacological effects produced by these agents in isolated perfused rabbit lung. The results are more closely associated with inhibition of removal and/or non-specific retention of the radioligands examined." @default.
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- W2006251277 title "Uptake and displacement of [3H]dihydroalprenolol, [3H]epinephrine and [3H]clonidine in isolated perfused rabbit lung" @default.
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- W2006251277 doi "https://doi.org/10.1016/0006-2952(82)90340-9" @default.
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