Dihydroergocryptine: a pseudo-irreversible alpha-adrenergic antagonist in the guinea pig vas deferens

Journal Article · Sun Mar 01 04:00:00 EST 1981 · Res. Commun. Chem. Pathol. Pharmacol.; (United States)

OSTI ID:5394260

Wilberding, C A; Marks, B H

The ergot alkaloid, dihydroergocryptine, exhibits some of the characteristics of a competitive alpha-adrenergic antagonist. Dihydroergocryptine physiological antagonism is surmountable by high concentrations of alpha-adrenergic agonists and (/sup 3/H)-dihydroergocryptine readily binds and dissociates from crude membranes with the characteristics expected of an alpha-adrenoreceptor ligand. However, during physiological studies, dihydroergocryptine antagonism is not readily reversible by washing. To explain this apparently paradoxical behavior of dihydroergocryptine, the characteristic of (/sup 3/H)-dihydroergocryptine accumulation and efflux in the guinea pig vas deferens were studied. Vas deferens segments accumulated 0.99 pmol (/sup 3/H)-dihydroergocryptine/mg protein. Most of the radioligand was extractable by acid-ethanol. About 5-6% of the radioligand remained bound to extracted tissue residues and appeared to be associated with crude membrane fractions prepared from vas deferens segments. Kinetic analysis of (/sup 3/H)-dihydroergocryptine efflux from vas deferens segments indicated the presence of three compartments of radioligand in this tissue. A large compartment of (/sup 3/H)-dihydroergocryptine emptied slowly and may represent radioligand accumulated into the intracellular space. (/sup 3/H)-Dihydroergocryptine also was released from a compartment which exhibited the size and kinetics characteristic of alpha-adrenoreceptor sites on guinea pig vas deferens crude membranes. A small compartment of (/sup 3/H)-dihydroergocryptine was nonexchangeable and nonextractable by acid-ethanol; this nonextractable radioligand may be bound covalently to membrane sites and/or other tissue components.

• OSTI ID: 5394260
• Journal Information: Res. Commun. Chem. Pathol. Pharmacol.; (United States), Journal Name: Res. Commun. Chem. Pathol. Pharmacol.; (United States) Vol. 31:3; ISSN RCOCB
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ADRENALINE
ALKALOIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BINDING ENERGY
BODY
BUILDUP
CARDIOTONICS
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CHEMICAL ANALYSIS
CHEMICAL BONDS
DRUGS
ENERGY
ERGOTAMINE
GONADS
GUINEA PIGS
HORMONES
LABELLED COMPOUNDS
MALE GENITALS
MAMMALS
MEMBRANES
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHYSIOLOGY
QUANTITATIVE CHEMICAL ANALYSIS
QUANTITY RATIO
RADIONUCLIDE KINETICS
RODENTS
STEROID HORMONES
SYMPATHOLYTICS
SYMPATHOMIMETICS
TESTES
TRITIUM COMPOUNDS
VERTEBRATES