Identification of alpha 1-adrenergic receptors in cultured rat myocardial cells with a new iodinated alpha 1-adrenergic antagonist, [125I]IBE 2254.

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Abstract
The presence of .alpha.-adrenergic receptors in purified cultures of neonatal rat ventricular muscle cells was first confirmed pharmacologically and then demonstrated directly with a new iodinated .alpha.1-selective radioligand [125I]-I-2-[.beta.-(4-hydroxyphenyl)ethylaminomethyl]tetralone ([125I] IBE 2254). These cells respond to the .alpha.-adrenergic agonist phenylephrine with a positive chronotropic response that is markedly inhibited by the .alpha.1-selective antagonist, prazosin. The radioligand [125I] IBE 2254 binds to suspensions of intact cells rapidly (15 min), reversibly and with high specificity (80-85% inhibited by excess unlabeled BE 2254). As identified by [125I]IBE 2254, cardiac cells contain a homogeneous class of binding sites of high affinity (KD = 324 .+-. 42 pM) and limited capacity (33,000 .+-. 4000 sites/cell). Binding is stereoselective, as determined by the greater potency of l- than d-norepinephrine in competing for specific binding sites. Adrenergic antagonists compete with [125I] IBE 2254 in the order expected for binding to an .alpha.1-receptor (prazosin .simeq. IBE 2254 > phentolamine > yohimbine). The high specific binding observed with [125]IBE 2254, together with the inherently high specific activity of iodinated radioligands, suggests that [125]IBE 2254 will be a useful probe for the .alpha.1-adrenergic receptor in a variety of cell systems.