PubMed Health⌕ Search

Biomedical subjects

G Coruzzi

Publications and source records attributed to G Coruzzi.

At least 91 records · Page 5Linked to original sources
PubMed1989

Dihydropyridine receptors in the pregnant human uterus in vitro.

The stimulatory effect of the dihydropyridine derivative, Bay K 8644, on the isolated pregnant human uterus, and its interactions with the calcium channel blockers, nifedipine, verapamil and diltiazem and with the calmodulin inhibitor trifluoperazine were investigated. In uterine preparations showing spontaneous activity, Bay K 8644 (1 nmol/l-1 mumol/l) produced an increase in the frequency of contractions without effects on their amplitude. However, strong phasic contractions were induced in quiescent preparations. The stimulatory action of Bay K 8644 proved to be insensitive to calcium withdrawal, but was completely prevented in the presence of 1 mmol/l EGTA. Bay K 8644 shifted the inhibitory concentration-response curve of verapamil and nifedipine to the right, leaving the diltiazem- and trifluoperazine-induced effect virtually unchanged. Schild plot analysis revealed a competitive interaction of Bay K 8644 with nifedipine, while the interaction with verapamil was of the nonlinear type. These data demonstrated that the dihydropyridine derivative Bay K 8644 possesses calcium agonistic properties also in the isolated human uterus. Furthermore, the competitive interaction with nifedipine showed the existence of specific dihydropyridine receptors closely associated with the calcium channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Occurrence of specific receptors in the duodenum.

Three groups of receptors defined pharmacologically by means of specific agonists and competitive antagonists were described: receptors for the so-called gastrointestinal hormones, receptors for the autacoids and receptors for the neuromediators. Together with the better known post-synaptic receptors pre-synaptic ones were also discussed in the light of the different possible interactions between one and the other. The mode of action of drugs stimulating (agonists) or inhibiting (antagonists) the same receptors is so far a very intriguing problem. The availability of newer and more selective compounds capable of distinguishing not only different kinds of receptors but also the subtypes of a single class of receptors will certainly contribute to better understanding of this situation.

Duodenum↗
PubMed1989

Action of the new H2-receptor antagonist oxmetidine on the duodenum of different species.

The new H2-receptor antagonist, oxmetidine was studied for its effects on the motility of the duodenum of different species. Oxmetidine did not modify basal motility of the rat and guinea pig duodenum but it reduced or abolished the contractions elicited by different spasmogenic compounds (acetylcholine, BaCl2, KCl, eledoisin). In the rabbit duodenum, oxmetidine reduced in a dose-dependent fashion the basal motility. The effect of this compound appears to be indirect on the smooth muscle and not mediated through specific receptors. Experiments performed in Ca++-free and K+-depolarizing solution suggest that oxmetidine acts through interference with the transport and/or utilization of intracellular Ca++ions.

Animals↗
PubMed1988

Inhibitory effect of misoprostol on gastric acid secretion in vitro. Qualitative differences from natural prostaglandins.

The synthetic PGE1 analog, misoprostol, was shown to have a marked inhibitory effect on gastric secretion as determined in the isolated gastric fundus from immature rats. It inhibited both the unstimulated and pentagastrin-stimulated acid secretion at 10(-7)-10(-4) molar concentrations. Its effect was different from that of PGE1 and PGE2, which did not affect basal acid secretion (up to 3 x 10(-5) M), although they inhibited to the same extent as misoprostol the pentagastrin-induced acid secretion. When given by "mucosal" application, misoprostol (10(-7)-10(-5) M) behaved similar to the mast cell stabilizer, compound FPL 52694, but its maximum reduction response was only 50%. The above data suggest that misoprostol has additional antisecretory mechanisms of action not shared by the classical natural prostaglandins.

Alprostadil↗
PubMed1988

Pre- and postjunctional effects of histamine on the guinea pig urinary bladder: evidence for heterogeneity in the H1-receptor population?

Histamine was tested on the guinea pig isolated urinary bladder to determine both the direct effect on the muscle and the influence on the contractions induced by field stimulation. Histamine (10(-7)-10(-3) M) caused contraction of the bladder and enhancement of the atropine-resistant response to field stimulation. These effects were sensitive to the H1-receptor antagonist pyrilamine (pA2 = 8.55 and 7.07, respectively). The H2-antagonists cimetidine and famotidine were ineffective on both parameters. It is concluded that predominantly H1-receptors are present in the guinea pig urinary bladder and that they are localized both on the muscle and on non-cholinergic nerve terminals. The significant difference between the pA2 values for pyrilamine is likely to suggest a heterogeneity in the H1-receptor population.

Animals↗
PubMed1988

Effect of glucagon on gastric acid secretion by the isolated fundus from immature rats.

The effect of glucagon was studied on the isolated gastric fundus from immature rats in comparison with histamine. Glucagon (10(-7) -3 X 10(-6) M) caused a concentration-dependent increase in acid output, being approximately 25 fold more potent than histamine (ED50 values were 6.38 X 10(-7) M and 2.42 X 10(-5) M for glucagon and histamine, respectively). These compounds, however, did not differ in regard to the maximum response. The stimulatory effect of glucagon was not enhanced by pretreatment with 3 X 10(-8) M forskolin or 10(-7) M ICI 63197, a phosphodiesterase (PD) inhibitor. Conversely, both forskolin and ICI 63197 shifted to the left the concentration-response curve to histamine. The increase in acid secretion by glucagon was reduced by PGE1 (10(-5) M) and PGE2 (10(-5) M) but only PGE2 inhibited the response to histamine. From these data it can be concluded that glucagon stimulated acid production in the stomach from immature rats, and this effect does not seem to involve the same adenylate cyclase activated by histamine.

Animals↗
PubMed1988

Regulation of receptors on parietal cells on acid secretion.

Four types of receptors have so far been identified on the parietal cell: receptors for gastrin, acetylcholine, and histamine, whose activation leads to stimulation of acid secretion, and receptors for prostaglandins of the E series, whose activation leads to inhibition of acid secretion. Postreceptor events following drug-receptor interaction include mobilization of calcium ions and cAMP formation. Moreover, a number of putative receptors (for somatostatin, CCK, adenosine, secretin, etc.) have been hypothesized, even though definite evidence is still lacking. Finally, other substances may influence gastric acid secretion in a positive or negative way, but no evidence for an involvement of specific receptors on the parietal cells is available so far.

Gastric Acid↗
PubMed1988

Effect of forskolin on gastric acid secretion "in vitro": interaction with different secretagogues.

1. The effect of forskolin has been evaluated in the isolated gastric fundus from immature rats in comparison with other secretagogues. 2. Forskolin (10 nM-1 microM) caused an increase in acid production being more potent than histamine, dimaprit, bethanechol and DBcAMP and equipotent with pentagastrin and isoprenaline. 3. The response to forskolin was unaffected by ranitidine (1 microM), atropine (10 nM) and PGE1 (10 microM); conversely it was inhibited by omeprazole (3 microM). 4. Threshold concentration of forskolin (30 nM) enhanced the response to histamine, dimaprit and isoprenaline but not that to bethanechol and DBcAMP. 5. The above data confirm the strong gastric secretory activity of forskolin even in the early stage of development.

Animals↗
PubMed1988

Different effect of glucagon on gastric acid secretion in vivo and in vitro.

The effect of glucagon on gastric acid secretion was evaluated in conscious cats with gastric fistula and in the isolated gastric fundus from immature rats. Glucagon (10-25 micrograms/kg/h) caused a slight inhibitory effect on pentagastrin-induced acid secretion; in contrast it was ineffective against dimaprit. At these doses glucagon induced a marked increase in glucose plasma levels. In the isolated rat gastric fundus glucagon (10(-7) M-3 x 10(-6) M) induced a concentration-dependent increase in acid output, being approximately 100 times as potent as histamine. Conversely from histamine, glucagon was not affected by pretreatment with phosphodiesterase inhibitors, thus an involvement of cAMP seems to be unlikely.

Animals↗
PubMed1987

Receptors in the gastrointestinal tract.

The receptor concept has been recently evolved and a new science was actually created, namely "receptorology". Receptors are now identified by means of different techniques (binding, agonist-antagonist interaction, autoradiography, etc.). The new techniques allowed the investigators to define new receptors and new subtypes of the "classical" ones. In the gastrointestinal (GI) tract a number of receptors have been identified and localized both on the effector organ and in the nerve terminal where they exert an important modulatory function on the neurotransmitter release. Recent biochemical studies have allowed a better understanding of the post-receptor event involving the second or third messenger regulation. Particular changes of receptors were recognized and they allow us to consider receptors not as static entities but as very dynamic components of the plasma membrane capable of different kinds of alterations, like interconversion, internalization, mobility, up- and downregulation, etc. Together with the "classical" receptors (cholinergic, adrenergic, opioid, etc.) also new receptors were identified: different subtypes of receptors for the tachykinins, for prostaglandin of the E type in the gastric parietal cell and the so-called dihydropyridine (DHP) receptor in the calcium channel of different areas of the gut. It is obvious that the precise knowledge of receptors and of their agonists and antagonists will represent the basis for a more specific and efficacious treatment of various gastrointestinal disorders.

Adenylyl Cyclases↗
PubMed1987

Famotidine and ranitidine: any difference in the duration of action?

The new H2-receptor antagonist famotidine was studied to test its duration of action in comparison with ranitidine. In the conscious cat provided with gastric fistula famotidine and ranitidine, administered by bolus i.v. injection, by continuous infusion or intragastrically, had an inhibitory effect on dimaprit-induced acid secretion which lasted similarly. The only difference between the two compounds was the higher potency of famotidine. Reversibility studies carried out in the isolated gastric fundus from immature rats showed that famotidine, like ranitidine, was easily washed out even at the highest concentration tested (3 X 10(-6) M) and thus it can be considered a readily dissociable H2 antagonist in this tissue.

Animals↗
PubMed1987

Prostaglandins and acid peptic disease: state of the art.

A review of the new concepts concerning the regulation of acid secretion and the pathogenesis of peptic ulcer disease is presented. Advantages and disadvantages of the common pharmacological treatments are described with special emphasis on the drugs which represent, at present, the treatment of choice for peptic ulcer disease, namely, the histamine H2-receptor antagonists. The role of prostaglandins in health and disease is considered, and the possibility that synthetic compounds derived from natural prostaglandins represent a good alternative to the present medical management of peptic ulcer disease.

Gastric Acid↗
PubMed1987

Changes in duodenal contractility induced by "calcium antagonists" with different modes of action.

The inhibitory action of nifedipine, verapamil, diltiazem and trifluoperazine has been examined on isolated duodenum from rats and rabbits. On rabbit duodenum Ca2+ antagonists caused a reduction of the spontaneous motility in very low concentrations (10(-12)-10(-6)M). On rat duodenum Ca2+ antagonists inhibited the contractile response to BaCl2, CaCl2 and to field stimulation, nifedipine being the most potent compound (threshold concentration down to 10(-12)M). The above results indicated that Ca2+ antagonists can markedly alter the duodenal motility, both basal and drug-stimulated. The high potency of nifedipine and the selective antagonism by Bay K 8644 against nifedipine suggest the presence of a specific receptor for the dihydropyridines (DHP receptor) in the duodenum.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1986

Pharmacology of the novel H2 antagonist famotidine: in vitro studies.

The novel antiulcer drug famotidine was found to be a potent and selective inhibitor of histamine H2 receptors. Its activity on different parameters involving H2 receptors was higher than that of other compounds of the family: pA2 values were 8.33, 7.86 and 7.83 in the guinea pig atria, guinea pig papillary muscle and isolated rat gastric secretion, respectively. Apart from quantitative differences, famotidine differed from the other compounds, since it caused a competitive antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The duration of the inhibitory action on the "in vitro" gastric secretion resembled that of cimetidine and ranitidine. Famotidine was highly effective (approximately 10 times as potent as ranitidine) also on the rat uterus (unsurmountable antagonism) and on the guinea pig gallbladder (pA2 value = 7.71). Famotidine was apparently devoid of non-specific effects concerning the gastrointestinal motility even at very high concentrations (10(-4) M). In this respect, famotidine appeared to be more selective than cimetidine and ranitidine at the H2 receptor level. The high potency, the peculiarity of the antagonism and the lack of side-effects on a number of isolated preparations, indicate this H2 antagonist as a very peculiar member of the group.

Animals↗