Assessment of β-Adrenoceptor down Regulation in Man
A hormone, neurotransmitter or drug produces its effect by combining with a receptor site and initiating a series of changes which culminate in a measurable effect. Although it is well known that increasing the concentration of an agonist which stimulates a receptor will result in an increase in pharmacological effect it has only recently been recognized that changes in receptor function can also alter the magnitude of a pharmacological response. In addition, many drugs, hormones and neurotransmitters have been shown to regulate their own response through alteration in the function of the receptors to which they bind. Thus the magnitude of a response in any individual is dependent on both the concentration of agonist present and available for binding to the receptor site and the number of receptor sites on the effector cell. An increase in receptor number will produce an increase in the response to a given concentration of agonist, that is an increase in sensitivity, and may also produce an increase in the maximal response. Recently, the development of radiolabelled agonists and antagonists which have a very high specific activity has allowed the direct identification of receptors and studies of their function and control to be performed (Lefkowitz, Roth, Pricer & Pastan, 1970; Freychet, Roth & Neville, 1971; Conolly & Greenacre, 1977; Lefkowitz, Mukherjee, Coverstone & Caron, 1974; Aurback, Fedak, Woodjard, Palmer, Hauser & Troxler, 1974; Lefkowitz & Williams, 1977; Williams, Snyderman & Lefkowitz, 1976; Galant, Duriseti, Underwood & Insel, 1978; Newman, Williams, Bishopric & Lefkowitz, 1978).
KeywordsNoradrenaline Adrenaline Catecholamine Propranolol Tate
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