Expression of GTP Cyclohydrolase I (GTPCH) mRNA in the Rat: Tissue Distribution and Effect of Reserpine

Abstract

Disruption of vesicular monoamine storage by reserpine results in a marked depletion of monoamines in the central and peripheral nervous systems and a concomitant increase in tyrosine hydroxylase (TH) gene expression in response to the resulting acceleration of nerve impulse flow. This increase in TH mRNA appears to be catecholamine (CA) cell-type specific in that it is observed within NE-containing neurons of the locus coeruleus (LC), superior cervical ganglia (SCG) and adrenal gland or adrenal chromaffin cells but not in DA neurons of the substantia nigra (SN)^1,2. Tetrahydrobiopterin (BH4) is synthesized by three or four enzymes from GTP^3,4 and is the reduced pteridine cofactor required for CA and nitric oxide biosynthesis^5,6. GTP cyclohydrolase I (GTPCH) is the rate-limiting enzyme in this BH4 biosynthetic pathway^3,4. Few studies have examined GTPCH gene expression in monoamine-containing neurons. A full-length cDNA encoding GTPCH has been isolated from rat liver⁷. We have used the reverse transcription-polymerase chain reaction (RT-PCR) to clone a coding portion of this sequence from rat adrenal gland. With this clone we have performed an analysis of GTPCH mRNA in rat tissues by Northern blot and nuclease protection assay and have examined the expression of GTPCH mRNA in CA neurons of the peripheral and central nervous systems following a single reserpine injection.