Adrenergic regulation of alpha-MSH secretion in man: evidence for a stimulatory role of beta-receptors.

In several animal species the catecholamines stimulate the release of alpha-MSH from the melanotrope cells of the pituitary neurointermediate lobe through beta-receptors. The human hypophysis does not include a well-defined intermediate lobe and the methods for measuring alpha-MSH are often poorly sensitive. Neuroregulation of this hormone in man has thus received little attention. To see whether the adrenergic system is involved in the control of alpha-MSH secretion and whether the latter is independent of that of other peptides derived from proopiomelanocortin, such as ACTH, we studied the effects on plasma alpha-MSH-like immunoreactivity (alpha-MSH-LI), ACTH, and cortisol of some adrenergic drugs active on the beta-receptors. Six normal volunteers underwent the infusion of the following drugs: isoproterenol (0.03 microgram.kg-1.min-1 for 60 min), propranolol (1 mg.min-1 for 5 min followed by 0.1 mg.min-1 for 115 min), propranolol+isoproterenol (infused between 30 and 90 min of propranolol infusion), placebo (saline solution). Isoproterenol increased alpha-MSH-LI at 15 min (p < 0.001). Propranolol induced a fall of alpha-MSH-LI between 30 and 60 min (p < 0.001), followed by a return to preinfusion concentrations beginning at 75 min, and completely prevented the stimulatory effect of isoproterenol. Plasma ACTH and serum cortisol were always unaffected. These results indicate that in man the adrenergic system stimulates alpha-MSH-LI release through beta-receptors, and that alpha-MSH-LI secretion is dissociated from that of ACTH and cortisol. This in turn suggests that separate neuroregulatory mechanisms exist for the melanotrope and corticotrope cells.

Clonidine lowers alpha-MSH-like immunoreactivity in human plasma.

In a group of seven healthy subjects, the effects of acute intravenous administration of clonidine, a selective alpha 2 receptor stimulator, on plasma alpha-MSH-LI concentrations were measured. In comparison with saline, clonidine (0.075 mg) significantly reduced alpha-MSH-LI concentrations, with a maximum fall between 30 and 60 min., followed by a return to basal concentrations at 120 min.; no significant variations in plasma ACTH and cortisol were seen. The precise mechanism of this effect is unclear. Our study suggests that separate regulatory mechanisms exist for the secretion of POMC related peptides in the corticotroph and melanotroph cells of the human pituitary gland.

[Plasma beta-endorphin and caffeine consumption in chronic hemicrania]. / Beta-endorfina plasmatica e consumo di caffeina nell'emicrania cronicizzata.

Thanks to recent biochemical and neuroendocrine findings, migraine belonging to the group of primary headaches appears as a pathology of the antinociceptive system with evolutive character. It has been demonstrated, in fact, that right at the early stage of migraine, there is a significant reduction in liquoral concentrations of beta-endorphin (beta-E), endogenous opioid peptide followed by a similar change in the plasma opioid system. The opioid system deficiency is even more evident after stimulation tests that point to reduced reactivity of the hypothalamo-hypophyseal system with respect to stimuli that in normal subjects trigger hypophyseal beta-E incretion. Caffeine, a member of the methyl-xanthine group, is an interesting molecule in the study of migraine patients because the chronic intake of this substance, contained in numerous analgesics, has been related to the chronic nature of the pain. The purpose of the present study is to assess the relationship between caffeine consumption and plasma opioid system. With the administration of a single oral dose of caffeine, normal subjects present an increase in plasma concentrations of beta-E, while in patients with chronic migraine, the response is significantly lower. These data confirm the poor reactivity of the plasma opioid system to pharmacological stimuli in migraine. Average daily consumption of caffeine has also been determined. It was not possible to establish a correlation between consumption of caffeine and plasma concentrations of beta-E whether basal or after stimulus with caffeine.

Effects of chronic ethanol treatment on alpha-MSH concentrations in rat brain and pituitary.

Male Sprague-Dawley rats were chronically treated with a liquid diet containing 6.5% (v/v) ethanol or equicaloric sucrose. Rats were killed after 21 days of treatment. alpha-MSH-like immunoreactivity was measured in the intermediate lobe of the pituitary gland and in several brain regions. Chronic ethanol treatment significantly reduced alpha-MSH-like immunoreactivity in the pituitary gland; in the arcuate nucleus of the hypothalamus and in the substantia nigra. The results of this study confirm the earlier findings that chronic ethanol treatment reduces POMC biosynthesis in the pituitary gland and in the central nervous system.

Beta-endorphin-like and alpha-MSH-like immunoreactivities in human milk.

We measured with radioimmunoassay the beta-endorphin-like and alpha-MSH-like immunoreactivities in milk and plasma of 8 lactating women. Mean beta-endorphin concentrations ( +/- SD) were 16.6 +/- 6.7 fmol/ml in milk and 9.9 +/- 4.1 fmol/ml in plasma. alpha-MSH concentrations (mean +/- SD) were 39.4 +/- 15.5 pg/ml in milk and 18.2 +/- 8.4 pg/ml in plasma. The concentrations of both peptides in milk were significantly (p less than 0.05) higher than in plasma. No significant correlation between milk and plasma concentrations of these peptides was found.

Peripheral pharmacokinetic parameters of levodopa/carbidopa and the on-off phenomenon in parkinsonian patients.

The principal peripheral pharmacokinetic parameters of the levodopa/carbidopa association were investigated in 11 healthy volunteers and in 16 patients at various stages of Parkinson disease, with and without the on-off phenomenon. After oral administration of a standard dose of drug (levodopa 250 mg + carbidopa 25 mg) the peak plasma concentrations, peak onset time and area under the curve/time proved to be similar across the groups. There was no difference in peripheral pharmacokinetics of the association between parkinsonian patients with swings in response and those without.

Biogenic amines in cerebrospinal fluid and plasma of patients with dementia of Alzheimer type.

The involvement of monoaminergic neurons in Dementia of Alzheimer Type (D.A.T.) is still a matter for debate. In a selected group of patients with D.A.T. we evaluated monoamine levels in cerebrospinal fluid (CSF) and plasma and found a significant decrease in serotonin and dopamine metebolite levels. Dopamine levels were reduced in both CSF and plasma. Moreover, a significant correlation was found between the duration of the illness and the decrease in monoamine levels. These findings suggest that there is systemic damage to monoaminergic neurons in D.A.T.