The Influence of Dihydroergotoxine Mesylate on the Low-K Phosphodiesterase of Cat and Rat Brain <i>in vitro</i>

Abstract

Dihydroergotoxine mesylate (DHET; active substance of Hydergine®) was shown to be a stronger inhibitor of the low-K_m than of the high-K_m phosphodiesterase (PE) in cat and rat brain homogenates. The inhibition due to DHET was greater when a purified low-K_m PE preparation originating from a sonicated pellet (100,000 ¿r) of rat brain tissue was used. The drug alters the kinetic properties of the enzyme, producing a lowering of the negative cooperativity effect. This kind of PE inhibition is of particular importance at normal cellular cAMP levels, but does not interfere with cAMP production by hormonal stimulation.

Pharmacological Aspects of Dihydrogenated Ergot Alkaloids in Experimental Brain Research

“…This enables determination of lower turnover rates at lower substrate concentrations (i.c., to determine the low-Km PEase). period after 2 min Enzyme preparation of low-Km phosphodiesterase was performed according to the method of Enz et al (1978).…”