Neuropeptides, amines and amine receptors in the human spinal cord : the effects of Parkinson's disease
The aims of this study were to investigate (i) the levels of catecholamines, indoleamines, substance P and thyrotrophin-releasing hormone (TRH) in the post-mortem spinal cord of subjects who had died with Parkinson's disease and to compare them with those of control subjects (ii) adrenergic and serotonergic receptors in the post-mortem Parkinsonian and control spinal cord and (iii) the effects of subject age and sex and the interval between death and post-mortem (PMI) on the levels of neurotransmitters and neuropeptides and on receptor binding in post-mortem tissue. To perform these investigations (i) a sensitive radioimmunoassay which is specific for substance P and has low cross-reactivity with other similar peptides and (ii) a common extraction medium for the concomitant extraction of catecholamines, indoleamines, substance P and TRH from CNS tissue were developed. The main findings were: There were significant correlations between the levels of 5HT, TRH and α2-adrenoceptor binding and both subject age and the PMI. In Parkinson's disease compared with control subjects: (i) the levels of noradrenaline were significantly reduced in the thoracic ventral region of the spinal cord,(ii) dopamine levels were higher in the thoracic ventral and dorsal spinal cord,(iii) in the lumbar spinal cord 5HT levels were significantly reduced in the dorsal horn with an increase in the ratio of 5HIAA/5HT, (iv) noradrenaline levels were reduced in both dorsal and ventral horns of the lumbar spinal cord and (v) there were no differences between the levels of substance P and TRH in any spinal cord region. There were no measurable 5HT1A or 5HT2 binding sites in the human spinal cord under the conditions used. However, specific α2-adrenoceptor binding was defined in terms of binding affinity and number of receptors in the spinal cord.