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Y Salomon

Publications and source records attributed to Y Salomon.

At least 19 recordsLinked to original sources
PubMed1992

Melanocortins stimulate proliferation and induce morphological changes in cultured rat astrocytes by distinct transducing mechanisms.

Melanocyte stimulating hormone (MSH), adrenocorticotropic hormone (ACTH), and several peptides derived from pro-opiomelanocortin, are present in the dorsolateral hypothalamus and arcuate nucleus of several vertebrate species. These peptides affect central nervous system (CNS) functions including behavior, memory, and foetal brain development. In this study we investigated the effects of ACTH1-24, ACTH1-17, ACTH4-10, alpha-MSH, beta-MSH, and a potent analog (Nle4,D-Phe7)-alpha-MSH (melanocortins) on immunocytochemically defined astroglial cells prepared from primary cultures of 1-2-day-old rat brains. A cyclic adenosine 3',5'-monophosphate (cAMP) response to the melanocortins was only detected in astrocytes and not in other cell types in the culture. The extent of the cAMP response was greatest on day 21, the latest time tested. On the other hand, (methyl3H)-thymidine incorporation in astrocytes was significantly stimulated (1.5-2-fold) by melanocortins only in 7 and not in 14 and 21 day cultures. This mitogenic activity of melanocortins was not mimicked by other agents such as forskolin or isoproterenol which efficiently stimulate cAMP production in astrocytes. ACTH1-17 as a melanocortin representative induced significant morphological changes in 7 and 14 day cultures which included rounding of the cell body and process extension. This response, however, resembled that induced by forskolin and hence appears to be cAMP mediated. These findings suggest that astrocytes in the CNS may serve as a target for melanocortins. These peptides appear to affect differentiation and proliferation of these cells during certain developmental periods. While the morphological effects of melanocortins seem to be cAMP mediated, induction of proliferation of the astrocytes by melanocortins appears to involve an alternative signal transduction pathway.

Adrenocorticotropic Hormone↗
PubMed1991

Stimulation of cAMP and phosphomonoester production by melanotropin in melanoma cells: 31P NMR studies.

A major part of the present understanding of the molecular basis of signal transduction has been gained from in vitro studies using classical biochemical methods. In this study, we used 31P NMR spectroscopy to investigate the response of live M2R mouse melanoma cells to stimulation by melanocyte-stimulating hormone (MSH; melanotropin). In the presence of 3-isobutyl-1-methylxanthine and a synergistic dose of forskolin (1.67 microM), MSH induced a transient (approximately 60-min) rise in the cellular concentration of 3',5'-cyclic adenosine monophosphate (cAMP), which coincided in time with an equivalent decrease (approximately 40%) in ATP. However, no detectable change in phosphocreatine concentration was observed. Concomitantly, MSH induced a striking and unexpected increase in the concentration of three phosphomonoester (PME) metabolites (approximately 2-fold increase in total PME signal area); one signal has been assigned to phosphoethanolamine. The levels of the PMEs remained high for 2-4 hr and declined slowly (approximately 10 hr) to basal level, following perfusion with fresh culture medium. The increase in PME was also observed after stimulation with MSH alone. In contrast, stimulation with a high dose of forskolin (50 microM) and isobutylmethylxanthine (0.2 mM), although effective in stimulating the production of cAMP, did not induce the PME response. Evaluation of the cells' energetics indicated that the enhanced production of phosphoethanolamine is probably not due to ethanolamine phosphorylation. Therefore, it is likely to result from hydrolysis of phosphatidylethanolamine by a specific phospholipase C. The response of the PMEs appears to be regulated by a cAMP-independent process, suggesting the existence of an alternative transduction pathway controlled by MSH.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Heterogeneity of the MSH receptor among B16 murine melanoma subclones.

The heterogeneity of melanotropin receptors on B16 sublines was tested by using photoaffinity crosslinking techniques and the superpotent alpha-MSH derivative [Nle4, D-Phe7, 1'-(2-nitro-4-azido-phenylsulfenyl)-Trp9]-alpha- MSH (NAPS-MSH). Specific crosslinking of this compound to B16-F1, B16-F10, B16-M2R or B16-W4 cells revealed three different subtypes of MSH receptor based on SDS-PAGE analysis. Binding of monoiodinated alpha-MSH to these different subclones is saturable and characteristic for a single class of complexes (0.9 nM less than KD less than 1.6 nM). In this article the nature of the different MSH receptor subtypes as well as their possible correlation to the melanogenic potential of a particular cell line is discussed.

Affinity Labels↗
PubMed1990

The melanocortin receptor in the rat lacrimal gland: a model system for the study of MSH (melanocyte stimulating hormone) as a potential neurotransmitter.

The melanocortin receptors in intraorbital and extraorbital rat lacrimal glands were studied with [125I][Nle4,D-Phe7]alpha MSH as radioligand and with several unlabeled melanocortin peptides. The pharmacological properties of the melanocortin receptor in both tissues appeared to be essentially identical. Receptor binding was studied in a membrane fraction sedimented at 12,000-100,000 X g, establishing for [125I][Nle4,D-Phe7]alpha MSH a KD of 0.76 and 2.2 nM for the intra- and extraorbital glands, respectively. Binding of the radioligand was competitively inhibited by alpha MSH (alpha-melanocyte stimulating hormone) and ACTH-(1-24) with IC50 values in the submicromolar range. MSH binding in both tissues was abolished by EGTA and was increased dose dependently with elevation of free Ca2+ ion concentration. The half-maximal effect on MSH binding was obtained around 200 microM Ca2+ and maximal binding was reached at nearly 2 mM free Ca2+ in membrane preparations from both tissues. The calmodulin-binding peptides, melittin, mastoparan and M5, the latter being the 18-amino acid synthetic analogue of the C-terminal calmodulin-binding domain of myosin light chain kinase, inhibited MSH binding in the concentration range of 1-20 microM. Macroscopic autoradiographic analysis of cryosections prepared from either lacrimal gland to which [125I][Nle4,D-Phe7]alpha MSH was subsequently bound, showed the melanocortin receptor to be uniformly distributed within the acinar lobes. At the microscopic level, MSH was found to be associated with the acinar cells, primarily at the basal perinuclear region. Peroxidase secretion from extraorbital lacrimal slices was stimulated by MSH, epinephrine and carbamylcholine to a similar extent. The response of the tissue to stimulation by MSH was however not blocked by alpha/beta-adrenoceptor blockers or by atropine, suggesting that MSH acts as a primary secretagogue in this tissue. Thus, this system seems to be uniquely suited to serve as a model for the study of both the molecular and pharmacological details of the action of MSH and other melanocortins in a non-melanogenic tissue.

Animals↗
PubMed1979

Heparin inhibits PGE1-sensitive adenylate cyclase and antagonizes PGE1 antiaggregating effect in human platelets.

PGE1-sensitive adenylate cyclase in human platelet lysates in inhibited (50%) by heparin (10 microgram/ml). Inhibition is of a mixed type when analyzed by double-reciprocal analysis. It is also shown that heparin (2.5 to 10 microgram/ml) effectively antagonizes the antiaggregating effect of PGE1 on ADP-induced platelet aggregation. The possibility that heparin may exert its platelet-aggregating activity through inhibition of PGE1-sensitive AC in human platelets is discussed.

Adenylyl Cyclase Inhibitors↗
PubMed1978

Modulation of adenylate cyclase activity by sulfated glycosaminoglycans. I. Inhibition by heparin of gonadotrophin-stimulated ovarian adenylate cyclase.

Heparin inhibits (I50 = 2 microgram/ml) the activity of luteinizing hormone and human chorionic gonadotropin-stimulated adenylate cyclase in purified rat ovarian plasma membranes. Unstimulated enzyme activity and activity stimulated by NaF, GTP or guanosine 5'-(beta,gamma-imido)triphosphate were inhibited to a lesser extent. Human chorionic gonadotropin binding to this membrane preparation was inhibited by heparin (I50 = 6 microgram/ml). The inhibition with respect to hormone concentration was of a mixed type for hormone binding and adenylate cyclase stimulation. Inhibition by heparin was not eliminated at saturating hormone concentration. The degree of inhibition was unaffected by the order in which enzyme, hormone and heparin were introduced into the assay system. Heparin (3 microgram/ml) did not affect the pH activity relationship of basal and hormone-stimulated adenylate cyclase activity and did not change the dependence of enzyme activity on magnesium ion concentration. The inhibitory action of heparin cannot be solely attributed to interference with either catalysis or hormone binding. The possibility is considered that the highly charged heparin molecule interferes with enzyme receptor coupling, by restricting the mobility of these components or by effecting their conformation.

Adenylyl Cyclases↗
PubMed1978

Modulation of adenylate cyclase activity by sulfated glycosaminoglycans. II. Effects of mucopolysaccharides and dextran sulfate on the activity of adenylate cyclase derived from various tissues.

Heparin was found to be the most potent inhibitor of rat ovarian luteinizing hormone-sensitive adenylate cyclase (I50 = 2 microgram/ml) when compared to other naturally occurring glycosamin oglycans. This inhibition was also apparent when this enzyme was stimulated by follicle-stimulating hormone or prostaglandin E2. Heparin was also found to inhibit glucagon-sensitive rat hepatic adenylate cyclase, and the prostaglandin E1-sensitive enzyme from rat ileum and human platelets. In contrast, heparin stimulated the dopamine sensitive adenylate cyclase from rat caudate nucleus. The sulfated polysugar dextran sulfate exerts similar effects on adenylate cyclase activity of the rat ovary and was shown to inhibit hormone binding to rat ovarian plasma membrane in a manner similar to that exerted by heparin. In contrast to heparin, dextran sulfate inhibited dopamine-sensitive adenylate cyclase from rat caudate nucleus.

Adenylyl Cyclases↗
PubMed1978

The effect of outside work on the menopausal woman.

1,148 women between the ages of 45 and 54 from five different ethnic groups in Israel, representing a traditional-modern continuum were investigated with regard to the relationship of their menopausal symptomatology with their work situations now and what they were when the women were aged 40. A relatively low symptomatology was found among European Jews, North African Jews and Arabs in the peri- or postmenopause where their work load was unchanged or somewhat more than before. On the other hand, the Persian Jews showed a remarkable contrast, namely: those who had never worked at all outside the home suffered less than all the others in all the stages of menopause. These results cannot be explained only by the socioeconomic differences between the five groups, as the North Africans and Persians both belong to the lower urban socioeconomic class and the Arabs to the low rural socioeconomic class, with the Europeans belonging to the middle urban class. Nor can the results be explained merely by the difference in modernity and traditionalism. The matter is more complicated, and additional factors such as physical health, marital relationships and general stability are almost certainly involved. The advice to "go out and work" which is so often given by medical practitioners to menopausal women is thus not always correct, and should not be given automatically.

Adolescent↗