Striatal tyrosine hydroxylase activity: multiple conformational kinetic oscillators and product concentration...

Samples from rat striate cortices, taken in triplicate at 2-min intervals from a supernatant maintained at 4 degree C, then assayed for 1 min at 37 degree C for tyrosine hydroxylase activity, manifested average amplitudes of time-dependent variation that were related to the level of mean velocity and were not influenced by changing temperature or pharmacological ligands. In contrast, the frequencies of variation manifested characteristic wavelengths of about 26, 7.5, and 5 min, and the relative proportions of those frequencies were changed by an increase in temperature and by certain drugs that are active in the dopamine system (D-amphetamine, haloperidol, and propranolol). Hypothetical, contemporaneous multiple quasi-stable states, each with a characteristic spectral frequency of fluctuation, are consistent with the appearance of reiterative enzyme saturation functions when supernatant and column-enriched preparations were examined within the physiological cofactor range over increasing substrate concentrations. Pharmacologically sensitive time distribution of multipole enzyme conformations, each a kinetic oscillator, determining product concentration frequencies, may be a mechanism by which drugs influence neurotransmitter periodicities in brain.