''Spare'' alpha 1-adrenergic receptors and the potency of agonists in rat vas deferens

Journal Article · Sat Dec 31 23:00:00 EST 1983 · Mol. Pharmacol.; (United States)

OSTI ID:7008211

Minneman, K P; Abel, P W

The existence of ''spare'' alpha 1-adrenergic receptors in rat vas deferens was examined directly using radioligand binding assays and contractility measurements. Alpha 1-adrenergic receptors in homogenates of rat vas deferens were labeled with (/sup 125/I)BE 2254 (/sup 125/IBE). Norepinephrine and other full alpha 1-adrenergic receptor agonists were much less potent in inhibiting /sup 125/IBE binding than in contracting the vas deferens in vitro. Treatment with 300 nM phenoxybenzamine for 10 min to irreversibly inactivate alpha 1-adrenergic receptors caused a large decrease in the potency of full agonists in causing contraction of this tissue and a 23-48% decrease in the maximal contraction observed. Using those data, equilibrium constants for activation (Kact values) of the receptors by agonists were calculated. These Kact values agreed well with the equilibrium binding constants (KD values) determined from displacement of /sup 125/IBE binding. The reduction in alpha 1-adrenergic receptor density following phenoxybenzamine treatment was determined by Scatchard analysis of specific /sup 125/IBE binding sites and compared with the expected reduction (q values) calculated from the agonist dose-response curves before and after phenoxybenzamine treatment. This suggests that phenoxybenzamine functionally inactivates alpha 1-adrenergic receptors at or near the receptor binding site. These experiments suggest that the potencies of agonists in activating alpha 1-adrenergic receptors in rat vas deferens agree well with their potencies in binding to the receptors. The greater potency of agonists in causing contraction may be due to spare receptors in this tissue. The data also demonstrate that phenoxybenzamine irreversibly inactivates alpha 1-adrenergic receptors in rat vas deferens, but that the decrease in receptor density is much smaller than that predicted from receptor theory.

• Research Organization: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia
• OSTI ID: 7008211
• Journal Information: Mol. Pharmacol.; (United States), Journal Name: Mol. Pharmacol.; (United States) Vol. 25:1; ISSN MOPMA
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MALE GENITALS
MAMMALS
NEUROREGULATORS
NORADRENALINE
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPES
RADIORECEPTOR ASSAY
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STEROID HORMONES
SYMPATHOLYTICS
SYMPATHOMIMETICS
TRACER TECHNIQUES
VERTEBRATES