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The characteristics of alpha 1-adrenergic receptors were investigated in perfused rat hearts at 37 degrees C. [3H]Prazosin was bound in a time-dependent manner and reached equilibrium at 15 min. Scatchard analysis of the specific binding isotherm for [3H]prazosin indicated a population of high affinity sites (Kd = 0.41 nM, Bmax = 13.2 pmol/g wet wt). Prazosin binding was displaced by epinephrine as well as by the adrenergic antagonists prazosin greater than phentolamine greater than yohimbine greater than propranolol. Specific prazosin binding was defined as that portion of the binding inhibited by 10 microM phentolamine; phentolamine and epinephrine displaced 3H-prazosin to the same level. [3H]Prazosin was not metabolized by the heart. When pre-labelled hearts were perfused at 37 degrees C with prazosin-free medium non-specific binding of [3H]prazosin decreased more rapidly (t0.5 = 4 min) than specific binding (t0.5 = 38 min). Perfusion of the heart at lower temperatures (less than 10 degrees C) decreased the rate of loss of nonspecific binding and prevented the loss of specific binding. Fractionation of [3H]prazosin perfused hearts at 0 degrees C, when dissociation was minimal, led to a loss of binding so that sarcolemma-enriched fractions contained approximately 2% of the binding sites present in the perfused heart. The binding characteristics of sarcolemma-enriched fractions (Kd 0.10 nM, Bmax 300 fmol/mg protein) differed significantly from those of the perfused heart. Exposure of the heart to 10 min of ischaemia prior to binding studies did not alter the characteristics of the [3H]prazosin binding sites. It is concluded that the perfused rat heart contains a population of alpha 1-adrenoceptors which differ from those of isolated sarcolemma preparations perhaps because of alterations that occur during sarcolemma isolation. The perfused heart should be an appropriate model system in which to study the relationship between receptor occupancy and biological response as well as the direct effects of perturbations such as ischaemia.
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