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G Demontis

Publications and source records attributed to G Demontis.

10 recordsLinked to original sources
PubMed1999

G protein-linked receptors: pharmacological evidence for the formation of heterodimers.

By means of the expression of two chimeric receptors, alpha(2)/M(3) and M(3)/alpha(2), in which the carboxy-terminal receptor portions, containing transmembrane domains VI and VII, were exchanged between the alpha(2C)-adrenergic and the M(3) muscarinic receptor, it has been shown that G protein-coupled receptors are able to interact functionally with each other at the molecular level to form (hetero)dimers. In the present study, we tested the hypothesis that interaction between two different muscarinic receptor subtypes can lead to the formation of a heterodimeric muscarinic receptor with a new pharmacological profile. Initially, muscarinic M(2) or M(3) wild-type receptors were expressed together with gene fragments originating from M(3) or M(2) receptors, respectively. Antagonist binding, performed with pirenzepine and tripitramine, revealed the presence of two populations of binding sites: one represents the wild-type M(2) or M(3) receptors, the other the heterodimeric M(2)/M(3) receptor. In another set of experiments, we constructed a point mutant M(2) receptor M(2) (Asn404-->Ser), in which asparagine 404 was replaced by serine. Although this receptor alone did not show any binding for N-[(3)H]methylscopolamine (up to 2 nM), when cotransfected with M(3), it resulted in the rescue of a high-affinity binding for tripitramine. These findings demonstrate that M(2) and M(3) muscarinic receptor subtypes can cross-interact with each other and form a new pharmacological heterodimeric receptor.

Animals↗
PubMed1989

Products of heme-catalyzed transformation of the arachidonate derivative 12-HPETE open S-type K+ channels in Aplysia.

In Aplysia mechanosensory neurons, the neuropeptide FMRFamide increases the opening of the background S-K+ channel. This action is mediated by activation of arachidonic acid metabolism. Arachidonic acid in Aplysia nervous tissue is transformed through the 12-lipoxygenase pathway to 12-HPETE, which undergoes further metabolism. In intact sensory cells, 12-HPETE simulates the FMRFamide response, raising the question of whether 12-HPETE is the messenger molecule ultimately acting on the S-K+ channel. Here we show that in cell-free (inside-out) patches from sensory cells, 12-HPETE fails to modulate the S-K+ channel, but in the presence of hematin (which catalyzes 12-HPETE metabolism), it triggers sharp increases in the channel opening probability. We also found that SKF-525A, an inhibitor of the cytochrome P450, reduces the response to FMRFamide, arachidonic acid, and 12-HPETE in intact cells. We conclude that a heme-catalyzed transformation of 12-HPETE is necessary and sufficient to promote the opening of the S-K+ channel and a heme-containing enzyme such as cytochrome P450 might play this key role.

Animals↗
PubMed1987

Sardinia, a high-risk area for multiple sclerosis: a prevalence and incidence study in the district of Alghero.

Findings from small descriptive studies carried out in the last few years in Sardinia suggest that this region is now of high rather than medium risk for multiple sclerosis. It is uncertain whether this high prevalence reflects a different approach in case finding over time or a true change in disease occurrence. We report the results of a prevalence and incidence survey conducted in the district of Alghero, a community of 78,000 people in northwest Sardinia. Based on data from 31 patients, the average annual incidence for the period 1971 through 1980 was 4.1 per 100,000. On December 31, 1980, the prevalence rate was 59 per 100,000. The results support the view that Sardinia is now a high-risk area for multiple sclerosis, and further suggest a rise in the occurrence of the disease in recent years.

Adolescent↗
PubMed1986

Incidence of multiple sclerosis in Macomer, Sardinia, 1912-1981: onset of the disease after 1950.

Intensive search of all cases of MS occurring in the Sardinian commune of Macomer since 1912 indicated that MS was absent up to the early 1950s. All 13 ascertained cases had clinical onset in the years 1952-1981. During this period, the average annual incidence was 4.8 per 100,000; the highest incidence was found in the period 1957-1961, slowly decreasing up to 1981. MS was probably introduced after 1945, when the centuries-old isolation of Macomer ended and the native population came into contact with individuals from high- and medium-risk areas.

Adult↗
PubMed1984

Serotonin and Retzius cell depress the hyperpolarization following impulses of leech touch cell.

Intracellular recordings from T mechanosensory cells of Hirudo medicinalis showed, as previously demonstrated, that repetitive firing is followed by a long-lasting hyperpolarization. Serotonin application at two concentrations (1 microM and 50 microM) depressed this hyperpolarization by up to 2/3; the effect was dose-dependent, long-lasting and reversible. Intracellular stimulation of giant serotonergic neurons (Retzius cells, Rz) mimicked serotonin perfusion: the effect was proportional to the number of spikes fired by Retzius cells. The combined use of intracellular iontophoretic injection of horseradish peroxidase and lucifer yellow indicated the possible sites of contact between Rz and T cells. The effect of serotonin, released by Rz cells, is discussed with respect to its possible physiological significance.

Animals↗
PubMed1981

Rapid changes in GABA binding induced by stress in different areas of the rat brain.

Rats habituated to handling preceding sacrifice have higher [3H]GABA receptor binding in different brain areas (cerebellum, frontal cortex, caudate nucleus) than naive animals. The increase in GABA binding in handling-habituated rats is due to an increase in the number of receptors (Bmax) with no changes in the affinity of GABA binding for its ligand (Kd). Foot shock causes a sudden fall in GABA binding in handling-habituated rats but does not, or only slightly, in naive ones. The results indicate that stress causes a rapid decrease in GABA receptor binding in the central system and that the GABA binding values which are usually considered as normal are, in fact, values decreased by the handling manoeuvers preceding sacrifice.

Animals↗