Dihydroergocryptine: a "pseudo-irreversible" alpha-adrenergic antagonist in the guinea pig vas deferens.
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 [3H]-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 [3H]-dihydroergocryptine accumulation and efflux in the guinea pig vas deferens were studied. Vas deferens segments accumulated 0.99 pmol [3H]-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 [3H]-dihydroergocryptine efflux from vas deferens segments indicated the presence of three compartments of radioligand in this tissue. A large compartment of [3H]-dihydroergocryptine emptied slowly and may represent radioligand accumulated into the intracellular space. [3H]-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 [3H]-dihydroergocryptine was nonexchangeable and nonextractable by acid-ethanol; this nonextractable radioligand may be bound covalently to membrane sites and/or other tissue components.
D000818:Animals; D001665:Binding Sites; D004088:Dihydroergotoxine / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D007700:Kinetics; D008297:Male; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014316:Tritium; D014649:Vas Deferens / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D014316:Tritium; D004088:Dihydroergotoxine; D004837:Epinephrine