Biomedical subjects
Publications and source records attributed to F Benfenati.
The Authors describe the effects of CB 154 (2.5 mg, per os) and naloxone (0.4 mg, i.m) on GH levels in normal man serum. Preliminary results point to a clear potentiation of GH release when the opiate receptor blockade is added to a dopamine receptor stimulation.
The effects of 2-Br-alpha-ergocriptine (CB 154, 2.5 mg per os) and naloxone (0.4 mg i.m.) as well as the interaction between these two drugs on insulin serum levels have been studied in six normal male volunteers. Both CB 154 and naloxone lower insulin serum levels, while a more clear-cut reduction is observed after CB 154 plus naloxone. These results are discussed in view of a possible involvement of dopaminergic and enkephalinergic systems in the control of insulin secretion at hypothalamic or pancreatic level.
The sterical requirements of dopamine (DA) receptors involved in the control of prolactin (PL) secretion have been analyzed by studying the effects of the administration of d- and l-sulpiride (25 mg i.v.) on PL serum levels in five normal male volunteers. Both d- and l-sulpiride cause a remarkable rise in PL serum levels, the only difference between the two drugs being the lower decay rate of hormone levels after the l-isomer. The results obtained are discussed in the frame of a possible low steric selectivity of DA receptors controlling PL secretion in the hyposthalamo-pituitary axis.
By means of a new photographic method to quantitate catecholamine fluorescence in tissue sections it has been possible to demonstrate a high dopamine (DA) turnover within the DA cell bodies of the midbrain. The medially located small-sized DA cell bodies of the A10 DA cell group has a very high DA turnover which was significantly different from that found in the laterally located medium-sized DA cell bodies of the A10 cell group. Thus, the mesolimbic DA pathways may be divided into two systems, the medial system having a very high DA turnover in their cell bodies which may reflect a high functional activity in this system.
Catecholamine levels and turnover have been analyzed in DA cell body and in terminal-rich areas of the midbrain, diencephalon, and forebrain 48 hr following a 2-week treatment with l-sulpiride and haloperidol. At this time interval behavioral supersensitivity to DA agonists has been demonstrated. No changes in DA turnover are found in the DA cell body groups A9 and A10 or in various DA terminals of forebrain, with a possible exception for the diffuse type of DA terminals in the tuberculum olfactorium where a reduction of DA turnover rate is observed. In the median eminence of the l-sulpiride-treated group, however, DA turnover increases are observed. It is suggested that the lack of amine turnover changes in most of the DA terminal systems of the brain is related to the development of DA receptor supersensitivity in both striatal and limbic areas, balancing the DA receptor blocking activity of the neuroleptic drugs still present in the tissue of the brain.
The effects of 2-Br-alpha-ergocryptine (2.5 mg/osM), clonidine (50 microgram, intramuscularly) and naloxone (0.4 mg, intramuscularly) as well as the interaction between naloxone and 2-Br-alpha-ergocryptine or clonidine on luteinizing hormone (LH) follicle-stimulating hormone (FSH), prolactin (PL) and thyroid-stimulating hormone (TSH) serum levels in normal man have been studied. 2-Br-alpha-ergocryptine and clonidine clearly reduce and naloxone tends to reduce PL serum levels. TSH levels are lowered by naloxone as well by clonidine plus naloxone. The results obtained point also to a possible different pattern of LH and FSH secretion after naloxone, that is after opiate receptor blockade. The clonidine effects on PL secretion are discussed in the frame of a possible adrenergic control of the release of this hormone.
The effect of the combined administration of either CB 154 (2.5 mg/osM) or L-DOPA (500 mg/osM) and naloxone have been studied in six normal male volunteers. Naloxone cause a clear-cut potentiation of CB 154 effects on human growth hormone (hGH) secretion and only a slight, statistically non-significant, potentiation of L-DOPA effects on hGH secretion. These results have been discussed in the light of morphofunctional findings showing possible interactions between dopamine (DA) systems and somatostatin-positive and enkephalin-positive nerve terminals.
The effects of (+)- and (-)-sulpiride on anterior pituitary hormone secretion (LH, FSH, PL, hGH, TSH) have been studied in five normal men. Both (+)- and (-)-sulpiride increase PL and TSH secretion and decrease LH and FSH secretion, whereas they do not seem to affect hGH secretion. These results are discussed in view of the different action of (+)- and (-)-sulpiride on DA receptors in the forebrain with respect to DA receptors involved in the control of anterior pituitary secretion.
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The effects of bromocriptine (CB-154, 2.5 mg po), clonidine (0.05 mg im) and naloxone (0.4 mg im), as well as the interaction between naloxone and CB-154 or clonidine on basal insulin secretion were studied in 6 normal men. Clonidine, naloxone and CB-154 plus naloxone lowered insulin plasma levels; CB-154 alone caused only a slight reduction, whereas clonidine plus naloxone did not affect insulin secretion. These results prove the existence of a complex neuroendocrine control of basal insulin secretion through dopaminergic, adrenergic and opiate mechanisms; they also suggest that the opiate inhibitory control of insulin release may be dissociated from the dopaminergic one, but may interact with the adrenergic one.
Morphometric techniques have been used to introduce criteria to objectively define transmitter-identified nerve cell groups and subpopulations of nerve cells within such groups. The present method is exemplified on two coronal sections of the midbrain, in which 5-HT immunoreactive nerve cell bodies have been visualized. The reliability of the method is shown by the fact that it makes it possible not only to recognize groups B7, B8 and B9 of Dahlström and Fuxe [5] but also to assess the existence of two subpopulations within group B7 as previously suggested by Fuxe and Jonsson [11] based on subjective evaluations. Furthermore, the suggestion could be made that a small assembly of 5-HT nerve cell bodies in the dorsal part of the mesencephalic tegmentum may form a new 5-HT cell group. Hence, the present method offers the advantage of assessing the existence of transmitter-identified nerve cell groups on the basis of objective criteria and to describe them in a quantitative fashion. Therefore, it allows quantitation of morphological changes occurring in transmitter-identified neurons under different experimental and pathological conditions.
The present method is exemplified on coronal sections of the medulla oblongata containing phenylethanolamine-N-methyltransferase (PNMT) immunoreactive nerve cell bodies and their processes and on coronal sections of the pons containing the locus coeruleus, where PNMT immunoreactive nerve terminals have been demonstrated together with the dopamine-beta-hydroxylase immunoreactive nerve cell bodies. Morphometric analysis of the processes (both length and branches) and of the nerve terminals involve as a first step the division of the area under study into squares 100 microns wide, which are superimposed on a Cartesian plane. The uniformity of the density distribution of the nerve terminals and the processes (branches or length) can be analyzed by Lorenz curves, which in a quantitative way can measure the degree of unevenness and thus represent a measure of concentration. A concentration index can therefore be calculated. By the use of the densitometric approach it also becomes possible to study the density distribution of the nerve terminals with the highest antigen contents. The present method will make it possible to quantitate morphological changes occurring in processes and nerve terminals of transmitter-identified neurons.
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