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Biomedical subjects

G Coruzzi

Publications and source records attributed to G Coruzzi.

At least 163 records · Page 9Linked to original sources
PubMed1979

[Action of TRH on gastrointestinal motility in vitro (author's transl)].

Thyrotropin-releasing hormone (TRH) was studied for its effects on some strips of the gastrointestinal tract in vitro. TRH showed to possess a certain stimulatory activity on proximal segments of the g.i. tract being approximately as effective as histamine. This motor activity of TRH is discussed taking into account a possible physiological role outside the brain.

Acetylcholine↗
PubMed1978

Assembly of the mitochondrial membrane system: mutations in the pho2 locus of the mitochondrial genome of Saccharomyces cerevisiae.

Two mutants of Saccharomyces cerevisiae which show a loss of mitochondrial rutamycin-sensitive ATPase activity are described. Although phenotypically similar to mutants of the mitochondrial locus pho1 [F. Foury and A. Tzagoloff (1976) Eur. J. Biochem. 68, 113-119], these mutants define a second ATPase locus on the mitochondrial DNA (designated pho2), which is genetically unlinked to pho1. Analysis of recombination in crosses involving multiple antibiotic resistance markers indicates that the locus is in the segment of the genome between ery1 and oli2, very close to oli1. In fact it is proposed that the oli1 and pho2 mutations are in the same gene. Supporting evidence for this proposal includes: 1. The analysis of marker retention in petite mutants shows that the oli1 and pho2 loci were either retained or lost together in all cases. 2. Recombination frequencies of 0.05% or less are observed in crosses between the oli1 and pho2 loci. 3. When rho+ revertants are isolated from the pho2 mutants they frequently are oligomycin resistant. 4. pho2 mutants have an altered subunit 9 of the ATPase complex.

Adenosine Triphosphatases↗
PubMed1978

[Action of some gastric antisecretory drugs on histamine H2-receptors (author's transl)].

A series of compounds endowed with gastric antisecretory activity were examined for their possible effects on histamine H2 receptors in different experimental conditions. The data obtained suggest that, apart from cimetidine, all the other compounds are devoid of antagonistic properties on H2 receptors. The inhibitory effect observed in some of the examined preparations is probably connected with unspecific actions.

Animals↗
PubMed1977

Action of some natural peptides on the stomach of the anaesthetized rat.

Different peptides of natural origin were studied for their stimulant activity on the stomach of the anaesthetized rat. The group of the tachykinins (substance P and its analogues) showed a noticeable spasmogenic activity on the whole stomach from the fundus to the pylorus. Threshold doses ranged between 0.1 and 5 microgram/kg by i.v. route and the order of potency was: eledoisin greater than phyllomedusin greater than physalaemin greater than uperolein greater than substance P. A good correlation between the dose and the duration of the spasmogenic effect was always observed and tachyphylaxis never occurred. Experiments carried out with different kinds of inhibitors suggested that tachykinins act directly on the smooth muscle of the stomach. Taking into account also results obtained in other experimental conditions it was possible to state that the N-terminal part of the molecule of these peptides has a certain importance in determining the degree of their potency in the different tests. The peptide motilin, which does not belong to the family from a chemical point of view, was scarcely active, if at all, in modifying the motility of the rat stomach.

Animals↗
PubMedDate not supplied

Control of gastric acid secretion by histamine H2 receptor antagonists and anticholinergics.

The control of gastric secretion may be obtained by means of several pharmacological compounds: histamine H2 receptor antagonists and anticholinergics are so far the most widely employed drugs in pharmacological experiments and in clinical practice. The H2 blockers are able to inhibit the secretory response to histamine, acetylcholine and gastrin; they are effective and safe and at present they have been employed in several million patients suffering from diseases characterized by acid hyperproduction. The compounds available on the market are cimetidine, ranitidine, famotidine and nizatidine; however, approximately 11,000 compounds of the family have been synthesized and about 20 of these are under clinical evaluation. The blockade of H2 receptors is the primary action of these drugs; however, they possess also secondary actions which may represent untoward effects but in some cases may be actually useful (increase in prostaglandin synthesis, inhibition of LTB4 synthesis, etc.) The 'classic' anticholinergics appear to be decidedly less important mainly from a therapeutic point of view. However, the new compounds like pirenzepine and telenzepine, which block specifically the so-called M1 receptors located in the ganglia of the myenteric plexus, may represent an alternative to the H2 blockers since they are virtually devoid of the untoward reactions typical for the old atropine-like compounds (dry mouth, mydriasis, tachycardia, etc.) Both H2 blockers and the new antimuscarinic compounds may have effects not only on the parietal cells but also on other sites (G-cells, histaminocytes, D-cells) which control the function of the parietal cells themselves.

Animals↗
PubMedDate not supplied

Antisecretory activity of omeprazole in the conscious gastric fistula cat: comparison with famotidine.

The antisecretory activity of the H+/K+ ATPase inhibitor omeprazole was studied in the conscious gastric fistula cat in comparison with the H2-blocker famotidine. Omeprazole caused a dose-dependent inhibition of the dimaprit-induced acid secretion, being approximately fivefold less potent than famotidine (intravenous ID50S were 0.34 +/- 0.03 and 0.067 +/- 0.015 mumol/kg for omeprazole and famotidine, respectively). Omeprazole caused a non-competitive inhibition of the dose-response curve to dimaprit, whereas famotidine induced a parallel shift to the right without depressing the maximum response. Conversely from famotidine, the antisecretory effect of omeprazole was found to be dependent on the acid secretory state of the stomach, the effect being more evident when the compound was administered at the plateau of acid secretion. The inhibitory effect of omeprazole was very long lasting (25% inhibition was still present 24 h after administration of the drug) whereas that of famotidine was overcome by dimaprit infusion within 3-4 h. The antisecretory effect of omeprazole concerned to the same extent the volume and the acid concentration of the gastric juice, whereas famotidine reduced mainly the volume. When the stimulus was represented by pentagastrin the intravenous ID50 values were 0.57 +/- 0.03 and 0.088 +/- 0.015 mumol/kg for omeprazole and famotidine. respectively. From the above data it may be concluded that the antisecretory profile of omeprazole differed markedly from that of famotidine, independently from the potency and the efficacy of the two drugs.

Animals↗
PubMedDate not supplied

Characterization of the spontaneous motor activity of the isolated human pregnant myometrium.

The motor activity of myometrial strips from pregnant human uterus was characterized in vitro by the use of inhibitory compounds acting on the smooth muscle contractility at different levels. Spontaneous contractions were not inhibited by tetrodotoxin or a series of membrane receptor antagonists, like anticholinergics, antihistaminics, alpha-adrenergic blocking agents, antiserotoninergics and opioid receptor antagonists, thus excluding neuronal involvements or a local release of endogenous mediators active on the respective membrane receptors. The ineffectiveness of indomethacin (10(-5) M) minimizes a role for excitatory prostaglandins. Isoprenaline and selective beta 2-adrenergic stimulants, like salbutamol and hexoprenaline (up to 10(-5) M), failed to affect the amplitude of spontaneous contractions. Conversely the adenylate cyclase activator, forskolin, had a concentration-dependent inhibitory effect. Ca2(+)-free medium, trifluoperazine and all the calcium channel blockers examined produced a concentration-dependent inhibition of the spontaneous contractions in the following order of sensitivity: nifedipine much greater than verapamil much greater than diltiazem greater than trifluoperazine. The inhibitory effect of nifedipine was not overcome by excess calcium concentration in the bathing medium, but was completely restored by addition of the calcium agonist Bay K 8644 10(-7) M. From these data it can be concluded that the spontaneous activity of pregnant human myometrium in vitro is independent of neural or humoral mechanisms. The inhibitory effect of Ca(+)-free medium and the efficacy of calcium channel blockers support the view that calcium influx is an important step in initiating the contractile activity of uterine smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMedDate not supplied

SAR studies on H2 antagonists containing alkylamino substituted 1,2, 5-thiadiazole 1-oxide moieties.

A number of ranitidine analogues in which the diamino-1,2,5-thiadiazole 1-oxide substructure bearing alkyl chains of different length is present as the urea equivalent group, were synthesised and studied for their lipophilic and H2 antagonist properties. Derivatives which displayed a logP < or = 3 behaved as competitive antagonists of histamine at H2 receptors present on guinea pig right atrium. The remaining more lipophilic members of the series showed an insurmountable antagonism not completely reversible after prolonged washing. A binding study suggested that an increase in the length of alkyl chain gave rise to hydrophobic interactions with the receptor which were responsible for the apparent irreversible H2 antagonism shown by the higher homologues of the series.

Animals↗
PubMedDate not supplied

Synthesis of 1,2-benzisothiazole derivatives and investigation of their putative histaminergic activity.

Some new 2-(1,2-benzisothiazol-3-yl)ethylamine derivatives were synthesised and their putative histaminergic activity was investigated in in vitro gastrointestinal and cardiac preparations. In the isolated guinea pig duodenum, all the compounds induced a tetrodotoxin- and atropine-sensitive contractile activity, which was minimally affected by mepyramine in the case of the compound 2-(1,2-benzisothiazol-3-yl)ethylamine. In the same tissue, all the compounds were devoid of any H3 receptor agonistic or antagonistic activity, but caused a nicotinic and/or 5-HT3 receptor activation. None of these compounds induced any histamine H2 agonistic or antagonistic activity in the isolated guinea pig gastric mucosa or in the isolated papillary muscle. On this latter substrate, the compound N,N,N-trimethyl-2-(1,2-benzisothiazol-3-yl)ethylammonium iodide induced a positive inotropic activity, apparently due to a release of catecholamines. These results demonstrate the substantial inability of 1,2-benzisothiazole derivatives to interact with histamine receptors in functional tests. These compounds, however, possess gangliomimetic properties, related to the activation of 5HT3 and/or nicotinic receptors.

Animals↗
PubMedDate not supplied

Role of histamine H(3) receptors in the control of gastrointestinal motility. An overview.

Over the last few years, the biochemical and functional characterization of H(3) receptors has been a matter for extensive investigation, culminating in the cloning of the human, guinea pig and rat receptor protein from brain tissues. This discovery contributed to determine the distribution of receptors in the body and to define the molecular mechanisms which follow activation. The major breakthrough in the histamine H(3) receptor field came with the synthesis of selective and potent agonists and antagonists, which unravelled the function of this receptor subtype in the different tissues. As expected from the ubiquitous location of histamine in the body, histamine H(3) receptors have also been identified in virtually every tissue, although they are quantitatively less abundant than H(1) and H(2) receptors. Concerning the gastrointestinal tract, this new receptor subtype seems to have multiple cellular locations, which include neurons, enteric ganglia, paracrine and immune cells and, in some tissues, also smooth muscle cells. Therefore it might be regarded as a general regulatory system of different digestive functions, including motility. The effects mediated by histamine H(3)-receptors mainly reflect the presynaptic inhibition of the release of either excitatory or inhibitory neurotransmitters from the myenteric plexus. The molecular mechanism of presynaptic inhibition seems to involve a restriction of calcium entry into the nerve endings, but other mechanisms (reduction of cAMP), possibly associated to different H(3) receptor subtypes, may be involved. Despite the widespread distribution and the well defined inhibitory effects evoked in the majority of in vitro models of intestinal motility, no clear cut evidence of its involvement in the control of peristalsis could be provided. In vivo models of gastrointestinal transit, indeed, did not reveal a defined effect of histamine H(3) receptor ligands, even though the possibility of a central inhibition was pointed out in several studies. Therefore, it is not clear at the present what is the physiological meaning of the histamine H(3) receptor in the control of gastrointestinal motility and whether it could represent a potential target for novel therapeutic interventions in deranged motility, taking into account that human gastrointestinal tissues are apparently devoid of this receptor.

Animals↗
PubMedDate not supplied

Different mechanisms are responsible for the contractile effects of histaminergic compounds on isolated intestinal smooth muscle cells.

The effects of histamine and dimaprit on intestinal smooth muscle contractility were investigated on isolated cells from longitudinal muscle of the guinea pig ileum. Both histamine (10(-14)-10(-10) M) and dimaprit (10(-13)-10(-10) M) exerted a concentration-dependent contraction of intestinal cells, causing a maximum decrease in cell length of about 20%. This effect was not significantly different from that induced by cholecystokinin-octapeptide (CCK-8) 10(-9) M. The concentration-response curves to histamine and dimaprit were shifted to the left in the presence of the histamine H2-receptor antagonist famotidine (10(-7) M) indicating the occurrence in the smooth muscle of H2 receptors mediating relaxation. Whereas the contraction produced by histamine was competitively antagonized by the H1 receptor antagonist mepyramine (10(-8) M), neither mepyramine (10(-7) M) nor temelastine (10(-7) M) did modify the contractile effect of dimaprit. In contrast, atropine (10(-8) M) significantly depressed the maximum response to dimaprit without affecting that exerted by histamine. These data indicate that histamine and dimaprit can modify intestinal contractility, by acting via different mechanisms; while the contractile action of histamine is related to H1 receptor activation, that produced by dimaprit involves cholinergic pathways.

Animals↗