EFFECT OF 5, 6 DIHYDROXYTRYPTAMINE ON NITRIC OXIDE SYNTHASE IN DIFFERENT PARTS OF RAT BRAIN

Background: On the basis of structural relationships between 5,6 dihydroxytryptamine (DHT) (a neurotoxic analogue of serotonin) and physostigmine (eserine), this work aimed to study the in-vitro effect of DHT on nitric oxide synthase (NOS) obtained from whole and five different parts of rat brain, namely: basal ganglia, frontal cortex, medulla oblongata, pons and cerebellum.

Objectives: The study aimed to identify the inhibitory power of DHT on NOS enzyme and to find which parts of the brain were inhibited than the others.

Methods: Kinetic studies of the enzyme and the inhibitor were done. Constants characterizing this inhibition, namely, the bimolecular rate constant ka, the binding constant KB and the inhibition constant ki were done.

Results: It was found that NOS extracted from medulla oblongata (M.O), pons and cerebellum was inhibited more than that extracted from other parts and the inhibition of NOS by DHT in vitro was found to be of the competitive type. Constants characterizing this inhibition, namely, the bimolecular rate constant ka [14, 7 and 6.1 (µmol/L.min)-1 for M.O, pons and cerebellum respectively], the binding constant KB [0.4, 0.8 and 0.6 mmol/L], and the inhibition constant ki (5.5, 5.6 and 3.67 min-1) were determined.

Conclusion: The affinity of 5, 6 DHT (a neurotoxic analogue of serotonin) towards NOS extracted from pons and medulla oblongata was higher than the other parts. Those are the parts responsible for the vital centres.