The tetrodotoxin-binding component associated with the voltage-sensitive sodium channel from electroplax membranes of Electrophorus electricus has been purified. The toxin-binding site could be efficiently solubilized with Lubrol-PX, resulting in an extract of high initial specific activity.Purification was facilitated by the development of a rapid, quantitative binding assay. The binding component was stabilized during purification by the use of mixed lipid/detergent micelles of defined composition, and by the saturation of the site with tetrodotoxin.The purification was achieved by means of a highly selective adsorption of the toxin-binding component to DEAE-Sephadex A-25, followed by desorption at hig ionic strength and chromatography over Sepharose 6B. Final peak specific activities were at least 50% of the specific activity expected for a pure, undenatured toxin-binding component of 230,000 molecular weight.

SUMMARY Activation of renal a-adrenergic receptors induces vasoconstriction, proximal tubular reabsorption of sodium, and inhibition of renin release. Excesses of these effects are present in varying degrees in animal models of, and in patients with, "essential" hypertension. Since essential hypertension is genetically determined, we sought abnormalities of renal a-adrenergic receptors in the Okamoto-Aoki strain of spontaneously hypertensive rats (sr-SHR) and their stroke-prone variant (sp-SHR). Total a-adrenergic receptor concentrations were determined by Scatchard analysis of [ 3 H]dihydroergocryptine binding to a renal membrane fraction and were found to be increased (p < 0.02) in male sr-SHR at 4, 16, and 32 weeks of age and in female sr-SHR at 16 weeks of age as compared to age-and sex-matched Wistar-Kyoto controls. They were also increased in 9-week-old sp-SHR renal membranes (p < 0.005). Further studies revealed that this increase in renal a-adrenergic receptors was due entirely to an increase in a 2 -receptors as measured by [ radioligands could be demonstrated between any of the hypertensive and normotensive groups of rats. Plasma norepinephrine levels were elevated (p < 0.01) in the 4-, 9-and 16-week-old SHR, but not in the 32-week-old hypertensive rats. Thus, high renal a 2 -adrenergic receptor number is coupled with a significant increase in plasma norepinephrine concentrations during the development of hypertension in SHR. By mediating an enhanced receptor-coupled response, such as increased proximal tubular sodium reabsorption, this abnormality of renal a-adrenergic receptors may contribute to some or all of the pathophysiologic derangements leading to hypertension in SHR. (Hypertension 4: 881-887, 1982) KEY WORDS • renal • a-receptor • SHR • hypertension • radioligand T HE kidney contributes fundamentally to genetically determined hypertension in rats. For example, transplantation of normotensive rat kidneys to hypertensive rats prevents or reverses their hypertension.1 " 3 Alternatively, transplantation of hypertensive kidneys to normotensive rats induces high blood pressure. Two renal functional abnormalities are common to genetically hypertensive rats and, interestFrom the

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