Potentiation of drug-initiated adrenal tyrosine hydroxylase induction by diazepam.

Abstract

The increase in in vitro adrenal tyrosine hydroxylase (TH) activity caused by drugs which produce an increase in preganglionic nerve activity as a result of actions outside the central nervous system was increased by the administration of diazepam. However, other central nervous system depressants such as pentobarbital, phenobarbital and diphenylhydantion were not found to share this property. Adrenal enzyme induction provoked by isoproterenol and 6-hydroxydopamine was increased by diazepam administration, whereas that produced by reserpine or insulin was not altered. The enhanced adrenal TH activity produced by diazepam pretreatment and isoproterenol administration could not be attributed to an increase in intensity or to an altered body temperature. Administration of 5-hydroxytryptophan can antagonize the induction of adrenal TH produced by isoproterenol, however, it did not block the TH induction produced by concurrent administration of diazepam and isoproterenol. The effect of diazepam on adrenal TH induction may be the result of its ability to interfere with central nervous system amine containing nerve functions which modulate preganglionic nerve activity, but the particular neurotransmitter system involved has not been determined.