Relationship between the beta-adrenergic receptor and adenylate cyclase.

Reconstitution of hormone-sensitive adenylate cyclase activity with resolved components of the enzyme.

(±)[125Iodo]cyanopindolol (ICYP) is a radioligand which binds with an extraordinarily high affinity and specificity to β-adrenoceptors. In contrast to (±)[125Iodo]-hydroxybenzylpindolol (IHYP), the new ligand has neither affinity to α- nor to 5-HT-receptors. The dissociation constants of ICYP for β-adrenoceptors in various tissues range from 27 to 40 pM, thereby exceeding the affinity of IHYP by a factor of ∼ 3. ICYP does not discriminate between β1− and β2−. Therefore, the densities of the two receptor subtypes can be determined from competition curves of ICYP by drugs previously found to show in vitro selectivity for β1−adrenoceptors. The guinea pig left ventricle contains only β1− adrenoceptors, whereas in the lung tissue, the ratio of β1− to β2−adrenoceptors is 1 to 4. The calculated affinities of five β1− selective antagonists for β1−adrenoceptors were nearly identical in the ventricle and the lung. Kinetic studies of ICYP binding to guinea pig lung membranes indicated that the dissociation reaction consists of two components, a fast process (t
1/2=9 min) and a slower process (t
1/2=8.8 h). A mathematical treatment revealed two possibilities of interpretation: 1. Two forms of the receptor exist which are interconvertible. 2. The (+)- and (−)-enantiomers of ICYP dissociate with different rate constants. The low dissociation constant of ICYP in combination with its high specific radioactivity (2175 Ci mmole−1) allows binding studies to be carried out with small protein and ligand concentrations, e.g. 3 μg protein per assay in guinea pig lung membranes.

(+/-)[125Iodo] cyanopindolol, a new ligand for beta-adrenoceptors: identification and quantitation of subclasses of beta-adrenoceptors in guinea pig.

Dopaminergic receptors in the anterior pituitary gland. Correlation of [3H]dihydroergocryptine binding with the dopaminergic control of prolactin release.

Regulation of beta-adrenergic receptors by guanyl-5'-yl imidodiphosphate and other purine nucleotides.

Binding of (125I)iodohydroxybenzylpindolol to putative beta-adrenergic receptors of rat glioma cells and other cell clones.

Expression of genes for metabolism of cyclic adenosine 3':5'-monophosphate in somatic cells. beta-Adrenergic and PGE1 receptors in parental and hybrid cells.

H J Anderson

Papers

Binding of (125I)iodohydroxybenzylpindolol to putative beta-adrenergic receptors of rat glioma cells and other cell clones.

Expression of genes for metabolism of cyclic adenosine 3':5'-monophosphate in somatic cells. beta-Adrenergic and PGE1 receptors in parental and hybrid cells.

Hormonal control of cyclic AMP metabolism in parental and hybrid somatic cells.