Catecholamine Synthetic Pathway Research Articles

Differential ontogeny of three putative catecholamine cell types in the postnatal rat retina

The development of tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) in the rat retina was investigated using the indirect immunofluorescence technique. Two types of TH-positive cells were found. The first appeared at postnatal day 2, in the vitreal half of the inner nuclear layer (INL). Single fibres from these neurones, bifurcating in and innervating layer 3 of the inner plexiform layer (IPL) were seen at day 4. This first type of TH-positive cell was most numerous at day 15, but thereafter disappeared before adulthood. At day 5, a more intensely staining TH-immunoreactive neurone became visible, occupying a more proximal part of the INL, and projecting multiple fibres to layer 1 of the IPL. In contrast, PNMT-positive cells, in the vitreal half of the INL and in the ganglion cell layer (GCL), sending single varicose axons to layer 3 of the IPL, were first apparent only at day 10, achieving a disposition similar to that of the adult by days 15–16 postnatal. Analysis of adjacent sections stained with antibodies to TH and PNMT revealed that neither type of TH-positive neurone also contained PNMT-like immunoreactivity. It is concluded that although both of the rate-limiting enzymes of the catecholamine synthetic pathway are present in the developing rat retina, they occur in 3 mutually exclusive populations of neurones.

Regulation of catecholamine synthesis in rat brain synaptosomes.

Abstract— Catecholamine synthesis in synaptosomal preparations of rat striatum, cortex and brain stem was investigated. The striatum had much higher activity than either the cortex or brain stem. Equilibration of labelled tyrosine between tissue and incubation medium was completed within 2 min. The apparent Km of tyrosine hydroxylase (EC 1.14.3a) and of the overall catecholamine synthetic pathway were both approximately 5 ± 10−6m for tyrosine. The following amines were found to inhibit striatal dopamine synthesis: dopamine, 25% inhibition at 5 ± 10−7m; noradrenaline, 25% inhibition at 5 ± 10−6m;and serotonin, 30% inhibition at 10−5m. The catecholamine‐induced inhibition of synthesis was antagonized by pre‐incubation with cocaine. Increasing the potassium concentration from 5 to 55 mm caused a release of amines into the medium which was accompanied by a 40% increase in dopamine synthesis, when synthesis was measured during the first 5 min of exposure to elevated potassium. These results indicate that synaptosomal catecholamine synthesis is inhibited by increases in intra‐synaptosomal amine levels, and that short‐term exposure to depolarizing concentrations of potassium can increase synthesis.