Characterization of alpha-adrenergic receptor subtypes in the rat renal cortex. Differential regulation of alpha 1- and alpha 2-adrenergic receptors by guanyl nucleotides and Na.
We have used the subtype-selective radioligands [3H]prazosin (an alpha 1-adrenergic antagonist) and [3H]yohimbine (an alpha 2-adrenergic antagonist) to examine alpha-adrenergic receptors in rat renal cortical membranes. Under the conditions used in this study, [3H]prazosin bound only to alpha 1-adrenergic receptors, whereas [3H]yohimbine bound only to alpha 2-adrenergic receptors; the two radioligands were completely selective and did not bind to a common site. The ratio of alpha 2- to alpha 1-adrenergic receptors was about 3:1. Guanyl nucleotides decreased the affinity of epinephrine at both receptor subtypes, but this effect was greater at the alpha 2-receptor and, according to computer analysis, occurred through different mechanisms at the two receptor subtypes. NaCl decreased the affinity of epinephrine at both alpha-receptor subtypes; this effect was more Na+-selective at alpha 2- than at alpha 1-receptors. Guanyl nucleotides and NaCl were additive in decreasing the affinity of epinephrine at the alpha 1-receptor but were synergistic at the alpha 2-receptor. In addition, NaCl increased specific binding of [3H] yohimbine but had no effect on the binding of [3H]prazosin. This enhancement of [3H] yohimbine binding was Na+-specific and fully reversible, and represented an increase in maximal binding capacity. Although binding of epinephrine to both alpha 1- and alpha 2-receptors could be modulated by guanyl nucleotides, we were unable to detect inhibition by epinephrine of basal or hormone-stimulated adenylate cyclase activity. Thus, separate alpha 1- and alpha 2-adrenergic receptors can be detected in the rat renal cortex and binding to both receptor subtypes can be regulated by guanyl nucleotides and Na+ X Na+ may directly interact with alpha 2- but not alpha 1-adrenergic receptors in the renal cortex. Our findings with renal cortical membranes indicate that regulation of agonist binding at alpha-adrenergic receptor subtypes by guanyl nucleotides and Na+ is not limited to alpha 2-adrenergic receptors, as previously reported with other tissues.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006150:Guanine Nucleotides / Q000502:physiology*; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000378:metabolism*; D012964:Sodium / Q000502:physiology*; D015016:Yohimbine / Q000378:metabolism
D006150:Guanine Nucleotides; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D012964:Sodium; D000262:Adenylyl Cyclases; D011224:Prazosin