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Biomedical subjects

G Coruzzi

Publications and source records attributed to G Coruzzi.

At least 73 records · Page 4Linked to original sources
PubMed1993

Histamine H3-receptor-induced inhibition of duodenal cholinergic transmission is independent of intracellular cyclic AMP and GMP.

1. The inhibitory effect of the histamine H3-receptor agonist (R) alpha-methylhistamine on cholinergic neurotransmission was studied in the isolated guinea pig duodenum in the presence of different compounds which alter intracellular levels of cyclic nucleotides and of the G proteins blocker pertussis toxin. 2. The action of (R) alpha-methylhistamine on electrically-evoked contractions was not modified either by forskolin and isobutylmethylxanthine (which increase cyclic AMP) or by zaprinast and methylene blue (which increase and decrease, respectively intracellular cyclic GMP). Drugs affecting cyclic nucleotide levels were also ineffective against the inhibitory effect of the alpha 2 adrenergic agonist clonidine. 3. Pertussis toxin significantly reduced the maximum inhibition induced by (R) alpha-methylhistamine and clonidine, without influencing the effect of low concentrations of the above compounds; conversely it shifted to the right in a parallel way the inhibitory effect of adenosine. 4. These data suggest that H3-receptor-mediated inhibition of cholinergic transmission in the guinea pig duodenum is not linked to intracellular nucleotide changes. Moreover the signal transducing mechanism activated by (R) alpha-methylhistamine involves pertussis toxin both sensitive and insensitive G proteins.

1-Methyl-3-isobutylxanthine↗
PubMed1992

Histamine H3 receptors are not involved in the regulation of rat gastric secretion.

The effects of histamine H3 receptor activation [(R)alpha-methylhistamine] and blockade (thioperamide) on rat gastric secretion were determined in vivo and in vitro. (R)alpha-Methylhistamine (0.1-5 mumol/kg i.p.) did not modify secretory volume and acidity in pylorus-ligated rats; it did not affect basal acid secretion and the secretion stimulated by histamine, pentagastrin and 2-deoxy-D-glucose in the lumen-perfused stomach of anaesthetized rats, when administered by continuous infusion (0.01-1 mumol/kg/h) or bolus injection (0.05-25 mumol/kg). In this preparation, the H3 agonist increased acid secretion at doses of 3-25 mumol/kg i.v., the effect being antagonized by famotidine. In the isolated gastric fundus from immature rats both (R)alpha-methylhistamine (0.01-10 mumol/l) and thioperamide (0.01-1 mumol/l) were totally ineffective against both spontaneous and stimulated gastric secretion. These results suggest that histamine H3 receptors are unlikely to have a role in regulating gastric acid secretion in the rat.

Animals↗
PubMed1992

Furan and thiophene analogues of omeprazole.

Synthesis and structure of some analogs of the omeprazole containing furan and thiophene rings are reported. Their effects on the basal and the histamine-stimulated secretion were evaluated on the isolated rat stomach.

Animals↗
PubMed1991

Histamine receptors in isolated guinea pig duodenal muscle: H3 receptors inhibit cholinergic neurotransmission.

A series of histamine H3 receptor agonists and the H3 receptor antagonist thioperamide were tested in the isolated guinea pig duodenum, to investigate the role of this new receptor subtype in the intestinal contractility. At the same time the selectivity of the different compounds for the various histamine receptor subtypes was investigated. In the presence of famotidine (10(-6) M) and thioperamide (10(-5) M), histamine, N alpha-methylhistamine (NMH) and (R)-alpha-methylhistamine (alpha-MH) exerted a concentration-dependent contractile effect through activation of H1 receptors; the ratio of potency was histamine = NMH greater than alpha-MH (this last compound was approximately 500 times less potent). In the presence of pyrilamine (10(-6) M) and thioperamide (10(-5) M), histamine, dimaprit and impromidine caused a slight contractile effect, showing a high degree of tachyphylaxis; this effect was abolished by tetrodotoxin (10(-6) M) and by famotidine (10(-6) M). alpha-MH was ineffective up to 10(-4) M. The H2 receptor agonists dimaprit (10(-4) to 10(-3) M) and impromidine (10(-6) to 10(-5) M) caused a relaxant effect on the contraction elicited by acetylcholine (ACh), BaCl2 and electrical stimulation. This effect, which was unaffected by famotidine, was not mimicked by alpha-MH and not reversed by thioperamide (10(-5) M). In the presence of pyrilamine (109-6) M) and famotidine (10(-6) M), histamine, NMH and alpha-MH inhibited the twitch responses to electrical stimulation, with EC50 values of 1.17 x 10(-7), 6.76 x 10(-8) and 2.45 x 10(-8) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of substance P and related neurokinins on gastric acid secretion.

Substance P and a series of related neurokinins having various degrees of selectivity for tachykinin receptors have been studied for their effects on gastric acid secretion both "in vitro" and "in vivo". In the isolated gastric fundus from immature rats, substance P, the C-terminal heptapeptide of neurokinin A, NKA (4-10), [Arg]NKB and two synthetic analogues of NKA (4-10), namely, [beta-Ala8]NKA (4-10) and [Ala5]NKA (4-10) (compounds marked Men 10210 and Men 10209, respectively) had no effect on spontaneous secretion but enhanced the secretory response to histamine. All the different neurokinins were effective in the range of concentrations 10(-7) - 10(-6) M. In the conscious cat with gastric fistula, substance P dose-dependently increased basal acid secretion, whereas Men 10210 was absolutely ineffective. Men 10209 caused a slight increase in acid output which, however, was only 10% of that induced by dimaprit or pentagastrin. The secretory effect of dimaprit and pentagastrin was not affected by the different neurokinins, conversely the response to 2-Deoxy-D-glucose was slightly reduced by Men 10210 (10 nmol/kg/h). The above data suggest that the natural and synthetic neurokinins studied have negligible effects on gastric acid secretion, thus the gastro-protective effect observed in some experimental conditions is unlikely to be related to an antisecretory effect of these compounds.

Amino Acid Sequence↗
PubMed1991

Evidence that histamine H3 receptors are involved in the control of gastric acid secretion in the conscious cat.

In an attempt to assess the role of histamine H3 receptors in the control of gastric acid secretion, the effects of the selective histamine H3 receptor agonist, (R) alpha-methylhistamine and antagonist, thioperamide were evaluated in the conscious gastric fistula cat under basal conditions and against different stimuli. (R) alpha-methylhistamine (0.05-0.2 mumol/kg/h) was ineffective against spontaneous and dimaprit-induced acid secretion; it also did not reduce significantly pentagastrin-induced acid output, but caused a dose-dependent (0.05-0.1 mumol/kg/h) and significant inhibition of the acid response to 2-deoxy-D-glucose. Thioperamide (0.02-0.04 mumol/kg/h) did not modify spontaneous acid secretion, whereas it evoked a significant enhancement of the acid response to submaximal doses (50 mg/kg i.v.) of 2-deoxy-D-glucose. Thioperamide completely reversed the inhibitory effect of (R) alpha-methylhistamine against 2-deoxy-D-glucose-induced secretion, while leaving unaffected the inhibition induced by somatostatin. These data suggest that histamine H3 receptors may be involved in the control of acid secretion stimulated by indirectly acting secretagogues.

Animals↗
PubMed1991

Histamine H3 receptors regulate acetylcholine release from the guinea pig ileum myenteric plexus.

The effect of selective histamine H3-receptor agonists and antagonists on the acetylcholine release from peripheral nerves was evaluated in the guinea pig longitudinal muscle-myenteric plexus preparations, preloaded with (3H)choline. In the presence of H1 and H2 blockade, histamine (10(-7)-10(-4) M) and (R)-alpha-methylhistamine (10(-8)-10(-6) M) inhibited the electrically-evoked acetylcholine release, being (R)-alpha-methylhistamine more active than histamine, but behaving as a partial agonist. The effect of histamine was completely reversed by selective H3-blocking drugs, thioperamide and impromidine, while only submaximal doses of (R)-alpha-methylhistamine were antagonized. Furthermore, thioperamide and impromidine enhanced the electrically-evoked acetylcholine release. On the contrary, the new H3-blocker, HST-7, was found substantially ineffective, both as histamine antagonist and as acetylcholine overflow enhancer. These data suggest that histamine exerts an inhibitory control on the acetylcholine release from intestinal cholinergic nerves through the activation of H3 receptors.

Acetylcholine↗
PubMed1991

Review article: the histamine H3-receptor: a novel prejunctional receptor regulating gastrointestinal function.

This review examines the evidence for the existence in the gastrointestinal tract of a new subtype (H3) of histamine receptors, previously described in the central nervous system. Study of these receptors is facilitated by the availability of the highly selective agonist (R) alpha-methylhistamine and the selective antagonist, thioperamide. H3-receptors seem to exert negative control on gastric acid secretion evoked by indirect cholinergic stimuli: their localization is unclear but it seems to be outside the parietal cell. H3-receptors also seem to be located on cholinergic and non-adrenergic non-cholinergic (NANC) neurones of the myenteric plexus, where they negatively control the release of neurotransmitters.

Animals↗
PubMed1991

Light represses transcription of asparagine synthetase genes in photosynthetic and nonphotosynthetic organs of plants.

Asparagine synthetase (AS) mRNA in Pisum sativum accumulates preferentially in plants grown in the dark. Nuclear run-on experiments demonstrate that expression of both the AS1 and AS2 genes is negatively regulated by light at the level of transcription. A decrease in the transcriptional rate of the AS1 gene can be detected as early as 20 min after exposure to light. Time course experiments reveal that the levels of AS mRNA fluctuate dramatically during a "normal" light/dark cycle. This is due to a direct effect of light and not to changes associated with circadian rhythm. A novel finding is that the light-repressed expression of the AS1 gene is as dramatic in nonphotosynthetic organs such as roots as it is in leaves. Experiments demonstrate that the small amount of light which passes through the soil is sufficient to repress AS1 expression in roots, indicating that light has a direct effect on AS1 gene expression in roots. The negative regulation of AS gene expression by light was shown to be a general phenomenon in plants which also occurs in nonlegumes such as Nicotiana plumbaginifolia and Nicotiana tabacum. Thus, the AS genes can serve as a model with which to dissect the molecular basis for light-regulated transcriptional repression in plants.

Aspartate-Ammonia Ligase↗
PubMed1990

Effect of histamine on gastric acid secretion "in vitro": interference with endogenous prostaglandins.

The interference between histamine and endogenous prostaglandins (PGs) was investigated in the isolated gastric fundus from immature rats by evaluating the effect of nonsteroidal antiinflammatory agents (NSAIDs) on the acid response to histamine and the effect of histamine on PGs production by the gastric mucosa. Indomethacin (10(-5) M) and diclofenac (10(-5) M) caused a dose-dependent enhancement of the response to histamine, dimaprit and DBcAMP, but did not affect bethanechol-, isoprenaline- and forskolin-induced acid production. The enhancing effect of indomethacin was abolished in low Ca2+ medium. PGE2 and 6-keto PGF1 alpha levels in the mucosal solution were not modified by histamine, while being reduced by indomethacin. From these data it is concluded that endogenous PGs may negatively modulate the secretory response to histamine. However, a direct effect of the amine on cyclooxygenase to increase PGs synthesis seems to be excluded since histamine did not modify PGs levels in the mucosal solution.

Animals↗
PubMed1990

Ranitidine but not famotidine releases acetylcholine from the guinea pig myenteric plexus.

The effects of the histamine H2-receptor antagonists ranitidine and famotidine on acetylcholine release have been studied in the guinea pig myenteric plexus longitudinal muscle preparation incubated with [3H]-choline. Ranitidine (3 x 10(-5)-3 x 10(-4) M) dose-dependently increased the resting release of acetylcholine and that evoked by electrical stimulation. The effect was present only in strips perfused with 10(-5) M physostigmine. The effect of ranitidine was inhibited by tetrodotoxin and hexamethonium. Famotidine (10(-5)-3 x 10(-4) M) was totally ineffective in modifying both the resting release and that evoked by field stimulation. Ranitidine did not antagonize the inhibitory effect of oxotremorine, which specifically activates negative feedback mechanisms via presynaptic muscarinic receptors.

Acetylcholine↗
PubMed1990

Changes in the ionic environment may alter the kind of antagonism of some histamine H2-receptor blockers in the guinea pig papillary muscle.

The effect of changes in the composition of the bathing medium on the effect of histamine and histamine H2-receptor antagonists was investigated in the isolated guinea pig papillary muscle. Ringer or Krebs-Henseleit solutions were used as nutrient fluids. They mainly differed with respect to pH and to Mg2+ and H2 PO4- content. Whereas the effect of histamine was not altered by ionic changes, the antagonism by some H2 blockers was different in the two nutrient solutions. The insurmountable antagonism elicited by high concentrations (greater than or equal to 10(-6) M) of famotidine, oxmetidine and mifentidine in Ringer solution was converted to surmountable when these drugs were tested in Krebs-Henseleit solution. Conversely, the antagonism induced by ranitidine was surmountable in both solutions, and that induced by high amounts of Ioxtidine was insurmountable in both nutrient fluids. Results obtained in Ringer solution were not modified by pH adjustments or by the addition of ions present in Krebs-Henseleit medium. These results suggest that the interaction of histamine with H2 receptors in the guinea pig papillary muscle was not influenced by alterations in the ionic composition of the nutrient fluid, whereas the antagonism may be critically dependent on the ionic environment.

Animals↗
PubMed1989

Nutrient solution may alter the effect of the H2 blocker famotidine in the guinea pig papillary muscle.

The effect of different nutrient fluids (Ringer or Krebs) on the antagonism induced by the new H2 blocker famotidine against histamine was studied in the guinea pig isolated papillary muscle. The response to histamine was the same in Ringer and in Krebs solutions, as for threshold concentration and maximum response, conversely the antagonism induced by famotidine was found to be dependent on the nutrient fluid employed. It was competitive for low concentrations of the drug in both fluids, whereas the unsurmountable antagonism caused by higher concentrations in Ringer was reversed into a classical competitive one in Krebs. The potency of famotidine did not vary (pA2 values = 7.86 and 8.09 in Ringer and Krebs, respectively). The addition of PO4 or Mg++ to Ringer or the pH adjustment, in order to minimize the differences in the ionic content, did not modify the results obtained. The above data suggest that the antagonism by high concentrations of famotidine against histamine may be competitive or unsurmountable according to the nutrient fluid employed and stressed the importance of the ionic environment in the drug-receptor interaction.

Animals↗
PubMed1989

Increased parietal cell sensitivity after chronic treatment with ranitidine in the conscious cat.

The sensitivity of histamine H2 receptors of the gastric mucosa after one month treatment with ranitidine, administered daily (5 mg/kg i.m.), was checked in 5 conscious cats provided with gastric fistula. Basal acid secretion as well as the acid response to the H2 agonist dimaprit (60 micrograms/kg/hr) were studied before and at different periods after cessation of ranitidine treatment (1, 3, 7 and 14 days). Control experiments were carried out in 5 gastric fistula cats which received daily physiological saline for one month. Basal acid secretion in treated animals increased significantly (p less than 0.05) from 0.04 +/- 0.002 to 0.24 +/- 0.05 mEq H+/10 min. Also the response to dimaprit increased significantly (p less than 0.05) from 0.49 +/- 0.08 to 0.86 +/- 0.12 mEq H+/10 min. Seven days after cessation of treatment, both basal and stimulated secretion returned to pretreatment levels. In control cats no significant difference was noticed in basal and stimulated secretion at the beginning and at the end of the study.

Animals↗
PubMed1989

Pharmacological characterization of mare uterus motility with special reference to calcium antagonists and beta-2-adrenergic stimulants.

1. Uterine motility was studied in vitro in the myometrial tissue obtained from pregnant and non-pregnant mares. 2. The spontaneous contractions of the preparations were not modified by tetrodotoxin, by anticholinergics, antiadrenergics, histamine H1 and H2 blockers, antiserotoninergic and opioid antagonists; but disappeared in Ca2+ and Na+ free medium. 3. beta 2-adrenergic stimulants like salbutamol and hexoprenaline and the calcium channel blockers nifedipine and verapamil were effective inhibitors of the amplitude of phasic contractions (ID50S for salbutamol and nifedipine were 7.7 nM and 14.6 nM, respectively in oestrus preparations). 4. The above data indicated that the mare myometrium contractility in vitro is very sensitive to the action of beta 2 mimetic compounds and calcium antagonists; nifedipine, in particular, seems to be a very promising alternative to beta 2 stimulants in the tocolytic therapy.

Adrenergic beta-Agonists↗
PubMed1989

Effect of calcium-channel blockers and salbutamol on the isolated mare uterus--interaction with the calcium agonist Bay K 8644.

The effects of nifedipine, verapamil and diltiazem were investigated in the isolated mare uterus in comparison with salbutamol. All the calcium-channel blockers and salbutamol inhibited the spontaneous, KC1- and electrically induced contractions; nifedipine and salbutamol were the most potent compounds. The calcium agonist Bay K 8644 (10(-8)-10(-6) mol/l) competitively antagonized the inhibitory effect of nifedipine (pA2 value = 8.54 +/- 0.06), whereas it was only slightly or totally ineffective against verapamil, diltiazem and salbutamol. These results indicate that calcium-channel blockers are potent inhibitors of mare uterine motility in vitro and emphasize the importance of Ca2+-related mechanisms in the control of uterine smooth-muscle contractility. Moreover, the validity of Bay K 8644 as a tool to distinguish classes of calcium-channel antagonists is confirmed.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗