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1. Monoamine turnover and neuropeptide Y (NPY) levels were investigated in the central and peripheral nervous systems in adult male rats chronically treated with morphine. 2. The well-recognized biochemical alterations (serotoninergic turnover increased in the hypothalamus, hippocampus and striatum; dopaminergic turnover increased in the striatum and cortex; adrenaline levels decreased in the adrenal glands) were observed. 3. In addition, we observed a significant decrease of the NPY levels in the hypothalamus, the striatum and the adrenal glands. The observed changes were not reflected in plasma. 4. Our results contribute to the evidence that brain and adrenal monoamines and NPY could be involved in the mechanism of morphine tolerance and/or dependence.

Previous studies indicating the importance of catecholamine metabolism in neuroblastoma were briefly reviewed. Metabolic pathways were presented showing how the major urinary metabolites 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA) are formed from norepinephrine and from dopamine plus 3,4-dihydroxyphenylalanine (DOPA), respectively. For 289 neuroblastoma patients at the time of diagnosis, the urinary excretion of VMA was significantly elevated in 75%, and HVA was elevated in 80%. Periodic assay of these metabolites during the course of the disease revealed that the excretion trends were of prognostic value with 80-90% reliability. By contrast, when the excretion in only the initial urine specimens was considered, the survival rate was the same for patients with normal, and with significantly elevated, excretion. Review of the results of tracer studies aimed at elucidating the in vivo metabolic origins of the urinary metabolites suggested that a) in neuroblastoma, the catecholamines were largely inactivated by intracellular metabolism in the tumor cells; b) there was excess production and excretion of the norepinephrine precursors, DOPA and dopamine; and c) in the tumors of most neuroblastoma patients, the initial enzyme in catecholamine synthesis, tyrosine hydroxylase, had an activity comparable with that in normal adrenal glands. The importance of the metabolism of catecholamines in patients with neuroblastoma was stressed: a) The excretion of elevated levels of urinary catecholamine metabolites were useful in diagnosis and in following the course of the disease, and b) study of the catecholamine metabolism in these patients permitted examination of possible relationships between the activity of the enzymes involved in catecholamine synthesis and the malignancy of this tumor.

The relationship among neuropeptide Y (NPY), catecholamines and haemodynamics was assessed both at baseline and during inotropic intervention in patients with congestive heart failure. Eighteen patients with idiopathic dilated cardiomyopathy (left ventricular ejection fraction (LVEF) = 26± 10%) underwent both right and left catheterization. Haemodynamicparameters were recorded at baseline and during dobutamine infusion. To measure norepinephrine (NE), epinephrine (E) (nmol. l: radioenzymatic assay) and NPY (pmol. l: immunoradiometric assay) plasma concentrations, blood samples were drawn from the femoral artery and from the coronary sinus, both at baseline and during dobutamine infusion. At baseline, NPY concentration were 2·15±0·97pmol.l in the femoral artery and 1 ·97 ±0·63 pmol. l in the coronary sinus. Peripheral concentrations of NPY were, however, no different from those of patients without congestive heart failure: 2·4±2·7pmol. l. Peripheral NE concentration was correlated to haemodynamic parameters: L VEF (r= — 0·65; P<0·01), cardiac index (r = — 0·54; P < 0·05), L Vend-diastolic pressure (r= +0-59; P<005), while peripheral N PY and E concentrations were not. Dobutamine improved haemodynamics, since cardiac index increased by 30% and LV end-diastolic pressure decreased by 40% (P<0·01). Peripheral NE concentration decreased from 6·48 + 4·5 to 482 ±2·69 nmol. l(P<0·05) but there was no change in E (0·99±0·61 vs 1·04 + 0·74 nmol .l) or NPY concentrations (2·41 + 0·99pmol. l). In the coronary sinus, neither NE nor NPY concentrations changed during dobutamine infusion. Thus, low levels of peripheral and coronary sinus NPY concentrations may not render the action of circulating NP Y deleterious to failing hearts. NE but not NP Y is related to haemodynamic parameters. When sympathetic tone decreases, NE and NPY seem to have different patterns of release. However, NPY's local role in neurotransmission in the pathogenesis of congestive heart failure should not be ruled out. [ABSTRACT FROM PUBLISHER]