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Biomedical subjects

G Bertaccini

Publications and source records attributed to G Bertaccini.

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