Differential diagnosis between exudate and transudate in pleural effusion

We determined the relative contributions of endogenous gastrin, histamine and cholinergic tone to basal acid secretion in chronic fistula rats. Results were compared with those for acid secretion in pylorus-ligated rats. In chronic fistula rats, YM022 ?(R)-1-[2,3-dihydro-1-(2'-methylphenacyl)-2-oxo-5-phenyl-1 H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea? dose-dependently inhibited pentagastrin-stimulated acid secretion and abolished this secretion at 1 mumol/kg, s.c., but did not affect histamine- and carbachol-induced acid secretion even at 10 mumol/kg. In contrast, famotidine at 1 mumol/kg completely inhibited not only the acid secretion induced by histamine but also those by pentagastrin and carbachol. Furthermore, atropine abolished carbachol- and pentagastrin-stimulated acid secretion and significantly suppressed histamine-stimulated acid secretion at 0.1 mumol/kg. YM022 dose-dependently inhibited basal acid secretion. The YM022 dosage required to inhibit basal acid secretion is consistent with that required to suppress pentagastrin-induced acid secretion. Famotidine (1 mumol/kg) and atropine (0.1 mumol/kg) also abolished basal acid secretion. In pylorus-ligated rats, YM022 inhibited acid secretion in a dose-dependent manner; the inhibition at 1 mumol/kg, i.v. was 65%. No additional effect was observed when rats were dosed at 30 mumol/kg. Famotidine partially inhibited acid secretion in these rats, whereas atropine abolished this secretion. These results indicate that the major part of basal acid secretion in rats is attributable to endogenous gastrin via histamine- and cholinergic tone-dependent pathways. Moreover, pylorus ligation reduces the relative contribution of gastrin to acid secretion due to the activation of cholinergic tone.     

A study of the vascular and acid-secretory responses of the rat gastric mucosa to histamine

1. The effects of histamine on gastric mucosal blood flow in the presence and absence of gastric acid secretion were studied in the rat. 2. Histamine, in doses greater than those required to stimulate maximal acid secretion, caused a small increase in mucosal blood flow per unit acid output. 3. When acid secretion was inhibited by methyl analogues of prostaglandin E2, histamine reduced arterial blood pressure and gave a dose dependent rise in mucosal blood flow. 4. When acid secretion was inhibited by the histamine H2-receptor antagonists, burimamide and metiamide, histamine still increased mucosal blood flow. 5. The use of H1-receptor antagonists to inhibit the histamine-induced hyperaemia was made difficult by their vasodilator actions. 6. The selective histamine H2-receptor agonist, 4-methyl histamine, had no effect on arterial blood pressure in doses which stimulated acid secretion. The increase in mucosal blood flow which accompanied the stimulation of acid secretion was inhibited by the anti-secretory prostaglandins and H2-receptor antagonists. 7. The selective histamine H1-receptor agonist, 2-pyridyl ethylamine, had no effect on acid output but increased resting mucosal blood flow. 8. These results suggest that histamine H2-receptors, primarily concerned with acid secretion, and H1-receptors concerned with vasodilatation are both present in the rat gastric mucosa.     

Comparison between beta 3 and beta 2 adrenoceptor agonists as inhibitors of gastric acid secretion

In order to investigate the role of beta 3 adrenoceptors in the regulation of gastric acid secretion we studied the effects of compound SR58611A (a selective agonist for atypical beta adrenoceptors), alone or in combination with beta-adrenoceptor antagonists, in the gastric fistula of a conscious cat. The effects of SR58611A were compared with those of clenbuterol, a selective agonist for beta 2 adrenoceptors. Intravenous infusion of SR58611A (0.3-3 mumol/kg/h) caused a dose-dependent, but partial, inhibition of the acid secretory response to 2-deoxy-D-glucose 100 mg/kg i.v., maximum effect not exceeding 40%. Clenbuterol (0.03-0.1 mumol/kg/h) caused a similar effect (maximum inhibition about 50%) at doses approximately 30 times lower. The acid secretion induced by the histamine H2-receptor agonist dimaprit (1 mumol/kg/h) was minimally affected by both beta adrenoceptor agonists. The inhibitory effect of SR58611A (3 mumol/kg/h) on 2-deoxy-D-glucose-induced acid secretion was not modified by pretreatment with the non-selective beta 1- and beta 2-adrenoceptor blocker propranolol, administered at doses (1.5 mumol/kg iv) that completely blocked the inhibitory effect of clenbuterol (0.1 mumol/kg/h). In contrast, bupranolol (10 mumol/kg i.v.) (a drug endowed with beta 3 antagonistic properties) prevented the inhibitory effects of both SR58611A and clenbuterol. The present data provide functional evidence that, besides beta 2-, also beta 3-adrenoceptors can have negative effects on gastric acid secretion, particularly when it is stimulated by indirect stimuli, like 2-deoxy-D-glucose. This gastric antisecretory activity may represent an additional mechanism for the physio-pharmacological control of gastric acid secretion.     

Role of nitric oxide in regulation of gastric acid secretion in rats: effects of NO donors and NO synthase inhibitor

1. The role of nitric oxide (NO) in the regulation of acid secretion was examined in the anaesthetized rat. 2. A rat stomach was mounted in an ex vivo chamber, instilled with 2 ml of saline every 15 min, and the recovered sample was titrated at pH 7.0 against 0.1 N NaOH by use of an automatic titrator for acid secretion. Gastric mucosal blood flow (GMBF) was measured simultaneously by laser Doppler flowmeter. 3. Intragastric application of NO donors such as FK409 (3 and 6 mg ml[-1]) and sodium nitroprusside (SNP; 6 and 12 mg ml[-1]) as well as i.p. administration of cimetidine (60 mg kg[-1]), a histamine H2-receptor antagonist, significantly inhibited the increase in acid secretion in response to pentagastrin (60 microg kg(-1) h(-1), i.v.), in doses that increased gastric mucosal blood flow (GMBF). 4. Intragastric application of FK409 (6 mg ml[-1]) increased both basal and stimulated acid secretion induced by YM-14673 (0.3 mg kg(-1), i.v.), an analogue of thyrotropin-releasing hormone (TRH), but had no effect on the acid secretory response induced by histamine (4 mg kg(-1) h(-1), i.v.). 5. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg kg(-1), i.v.) did not affect basal acid secretion, but significantly potentiated the increase in acid secretion induced by YM-14673 and slightly augmented the acid secretory response to pentagastrin. 6. Both pentagastrin and YM-14673 increased the release of nitrite plus nitrate (NOx), stable NO metabolites, into the gastric lumen, and these changes were completely inhibited by prior administration of L-NAME (10 mg kg(-1), i.v.). 7. Pentagastrin caused an increase in luminal release of histamine and this response was significantly suppressed by intragastric application of FK409 (6 mg ml[-1]). 8. These results suggest that either exogenous or endogenous NO has an inhibitory action on gastric acid secretion through suppression of histamine release from enterochromaffin-like (ECL) cells.     

N alpha-methylhistamine inhibits intestinal transit in mice by central histamine H1 receptor activation

The effects of (R)alpha-methylhistamine and N alpha-methylhistamine on intestinal transit were examined in mice. The passage of a charcoal meal in the gastrointestinal tract was dose dependently inhibited by N alpha-methylhistamine (1-20 mg/kg i.p.), but not by a selective H3 receptor agonist (R)alpha-methyl-histamine (1-50 mg/kg i.p.). The inhibitory effect of N alpha-methylhistamine (20 mg/kg) was attenuated by pretreatment with H1 receptor antagonists (mepyramine 5 mg/kg i.p. or 5 micrograms i.c.v. and triprolidine 5 mg/kg i.p.), but not by cimetidine (10 mg/kg i.p.), zolantidine (5 mg/kg i.p.), a brain-penetrating H2 receptor antagonist, or thioperamide (5 mg/kg i.p.), a selective H3 receptor antagonist. The effect of N alpha-methylhistamine was also attenuated by combined treatment with phentolamine and propranolol (5 and 15 mg/kg s.c., respectively) and by pretreatment with 6-hydroxydopamine (20 mg/kg i.p., 2 days before). N alpha-Methylhistamine markedly decreased histamine turnover in the mouse brain. These findings suggest that intestinal transit is inhibited by N alpha-methylhistamine via stimulation of central H1 but not H3 receptors and that stimulation of the sympathetic system is involved in this effect.     

The effect of beta andrenoceptor stimulation of canine stomach on pentagastrin-stimulated histamine release

The effect of beta adrenergic agonist isoproterenol, infused directly into the gastrosplenic artery in anesthetized mixed-breed dogs, on pentagastrin-stimulated gastric histamine release was examined to clarify the potential mechanisms by which beta adrenoceptor stimulation results in gastric acid inhibition. Two doses of isoproterenol (3 and 10 ng/kg/min) were infused with pentagastrin; histamine and n(tau)-methyl-histamine concentrations were measured in arterial and gastric venous samples, and their gastric secretory rates were calculated. Both doses of isoproterenol decreased histamine-secretory rate to pentagastrin from a peak of 234 +/- 51.5 ng/min with vehicle to 17.7 +/- 4.2 ng/min with the 3 ng/kg/min dose of isoproterenol and to 8.6 +/- 2.9 ng/min with the 10 nk/kg/min dose of isoproterenol. The change in N(tau)-methyl-histamine-secretory rate paralleled the histamine-secretory rate. Concomitantly with the histamine-secretory rate, the effect of beta adrenoceptor agonist on gastric somatostatin secretion was also examined. The lower dose of isoproterenol stimulated somatostatin-secretory rate from 4.0 +/- 1.8 to 31.8 +/- 10.3 ng/min, and the higher dose of isoproterenol increased somatostatin-secretory rate from 6.0 +/- 3.1 to 61.5 +/- 21.5 ng/min, whereas isoproterenol potentiated pentagastrin-stimulated gastric somatostatin release. These data demonstrate that isoproterenol is a potent inhibitor of pentagastrin-stimulated gastric histamine release, and the mechanism may be related to the concomitant somatostatin release. Thus, the most likely mechanism by which beta adrenoceptor stimulation results in inhibition of gastric acid secretion is through down-regulation of gastric histamine release.     

Transient increase of blood histamine level induced by pentagastrin. Continuous monitoring by in vivo microdialysis

BACKGROUND: Since few studies of (penta)gastrin-induced histamine release from the gastric mucosa into blood has been performed, an effect of pentagastrin on histamine level of rat blood was examined by using the in vivo microdialysis method. METHODS: Pentagastrin was perfused through the microdialysis probe implanted into the jugular vein of urethane-anesthetized rats or in urethane-anesthetized, totally gastrectomized rats, and dialysis samples of blood were concurrently collected. Histidine decarboxylase (HDC) activities and histamine contents in the glandular stomach and gastric acid output after pentagastrin stimulation were also investigated. RESULTS: Pentagastrin induced a transient increase of blood histamine in a dose-dependent manner but failed to cause any increase of blood histamine in the totally gastrectomized rat. Pentagastrin also induced increases of the HDC activity in the glandular stomach and of the gastric acid output. The peak histamine level in blood occurred 40 min after pentagastrin perfusion, whereas the peak acid secretion occurred after 80-120 min and then leveled off. CONCLUSIONS: The transient increase of blood histamine induced by pentagastrin is attributable to the histamine released from enterochromaffin-like cells and could be monitored by using the in vivo microdialysis method.     

Anatomical variation in the rudimentary horns of a unicornuate uterus: implications for laparoscopic surgery

The effect of the beta3-adrenoceptor agonist [ N-[(2S)-7-ethoxycarbonyl-methoxyl-1,2,3,4-tetrahydronaphth-2-yl] (2R)-2-(3-chloro-phenyl)2-hydroxyethanamine hydrochloride] (SR58611A) on gastric acid secretion was investigated in conscious cats with a gastric fistula. Intravenous infusion of SR58611A (0.3-3 micromol/kg/h) caused a dose-dependent inhibition of the acid secretion stimulated by 2-deoxy-D-glucose (2DG), with a maximum reduction by 45%. The secretory effect of the histamine H2-receptor agonist dimaprit only tended to be reduced by SR58611A (3 micromol/kg/h). The inhibitory effect of SR5861 IA was not modified by the non selective beta1- and beta2-adrenoceptor antagonist propranolol (1.5 micromol/kg i.v.), but it was prevented by bupranolol (10 micromol/kg i.v.), a drug endowed with beta3-antagonistic properties. Both antagonists blocked the inhibitory effect of the beta2-adrenoceptor agonist clenbuterol (0.1 micromol/kg/h) on 2DG-induced acid secretion. These findings suggest that compound SR58611A inhibits gastric acid secretion in the conscious cat through activation of beta3-adrenoceptors insensitive to propranolol.     

Gastric acid secretory responses to graded intravenous doses of histamine in hookworm anemia

Dose-response curves for the effect of continuous infusion of histamine on gastric acid secretion were obtained in 10 patients with iron deficiency anemia due to hookworm infection. Each patient was studied with 4 doses (40, 60, 80 and 100 mug/kg/h) of histamine acid phosphate administered for 3 h, on separate days, in random fashion. The acid output increased with the dose of histamine, the maximal acid output was reached in all patients at the dose of 100 mug/kg/h. The dose of histamine when calculated according to body weight correlated well with the maximal acid output; the absolute dose of histamine had no correlation with the maximal acid response. The dose-response curve of stimulated acid output in anemia patients was much flatter than in control patients.     

Synergism between low-dose nicorandil and neuropeptides on adenosine-induced vasodepression in rats

The involvement of endogenous nitric oxide (NO) in the control of gastric acid secretion induced by some secretagogues was studied in the mouse isolated whole stomach. The gastric acid secretion induced by McNeil A-343 [4-[[[(3-chlorophenyl)amino]carbonyl]oxy]-N,N,N-trimethyl-2-butyn- 1-aminium chloride], a muscarinic M1 receptor agonist, pentagastrin or electrical vagus nerve stimulation was markedly inhibited by pretreatment with the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA). This inhibitory effect of L-NNA was reversed by L-arginine, but not by D-arginine. Histamine-induced gastric acid secretion was not influenced by treatment with L-NNA. Famotidine completely inhibited the gastric acid secretion induced by McNeil A-343, pentagastrin or electrical vagus nerve stimulation, showing that these stimulations induced gastric acid secretion mainly through histamine release from histamine-containing cells in the gastric mucosa. Moreover, the pentagastrin- and bethanechol-induced histamine release from gastric mucosal cells was significantly inhibited by L-NNA. The NO donor, sodium nitroprusside, at a concentration not affecting histamine-induced gastric acid secretion, increased the acid secretory response, and this response was inhibited by famotidine. These results suggest that endogenous NO is involved in the gastric acid secretion via histamine release from histamine-containing cells.     

Role of endogenous prostaglandins in secretin- and plaunotol-induced inhibition of gastric acid secretion in the rat

We investigated the role of endogenous prostaglandins in the inhibitory effect of exogenous secretin and the antiulcer agent plaunotol on gastric acid secretion in the rat. Intravenous infusion of secretin (0.05 CU/kg/h) and intraduodenal administration of the secretin-releasing agent, plaunotol (320 mg/h), resulted in significant inhibition of gastric acid secretion stimulated by intravenous infusion of pentagastrin (0.3 micrograms/kg/h), and this was accompanied by an increase in the prostaglandin E2 content of the gastric mucosa. Intraduodenal administration of plaunotol (320 mg/h) produced plasma secretin levels comparable to the levels achieved by intravenous infusion of secretin (0.05 CU/kg/h). Intravenous administration of prostaglandin synthesis inhibitor, indomethacin (2 mg/kg + 1 mg/kg/h), completely abolished both the inhibitory action of secretin and plaunotol on gastric acid secretion, and the increase in gastric mucosa prostaglandin E2 induced by secretin and plaunotol. The results indicate that endogenous prostaglandins play a significant role in the inhibitory action of exogenous and plaunotol-released endogenous secretin in the rat.     

Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist

Ciproxifan, i.e., cyclopropyl-(4-(3-1H-imidazol-4-yl)propyloxy) phenyl) ketone, belongs to a novel chemical series of histamine H3-receptor antagonists. In vitro, it behaved as a competitive antagonist at the H3 autoreceptor controlling [3H]histamine release from synaptosomes and displayed similar Ki values (0.5-1.9 nM) at the H3 receptor controlling the electrically-induced contraction of guinea pig ileum or at the brain H3 receptor labeled with [125I]iodoproxyfan. Ciproxifan displayed at least 3-orders of magnitude lower potency at various aminergic receptors studied in functional or binding tests. In vivo, measurement of drug plasma levels, using a novel radioreceptor assay in mice receiving ciproxifan p.o. or i.v., led to an oral bioavailability ratio of 62%. Oral administration of ciproxifan to mice enhanced by approximately 100% histamine turnover rate and steady state level of tele-methylhistamine with an ED50 of 0.14 mg/kg. Ciproxifan reversed the H3-receptor agonist induced enhancement of water consumption in rats with and ID50 of 0.09 +/- 0.04 mg/kg, i.p. In cats, ciproxifan (0.15-2 mg/kg, p.o.) induced marked signs of neocortical electroencephalogram activation manifested by enhanced fast-rhythms density and an almost total waking state. In rats, ciproxifan enhanced attention as evaluated in the five-choice task performed using a short stimulus duration. Ciproxifan appears to be an orally bioavailable, extremely potent and selective H3-receptor antagonist whose vigilance- and attention-promoting effects are promising for therapeutic applications in aging disorders.     

Regulation of H1-receptor coupling and H1-receptor mRNA by histamine in bovine tracheal smooth muscle

1. Pretreatment of bovine tracheal smooth muscle (BTSM) with histamine (1-100 microM, 1 h) induced a concentration-dependent desensitization of the contractile response to subsequently administered histamine, with a reduction of the maximum response of 72 +/- 8% (n = 5) following pre-exposure to 100 microM histamine. In contrast, concentration-response curves to the muscarinic agonist, methacholine were not affected following histamine pretreatment, indicating a homologous desensitization. Furthermore, concentration-response curves to NaF, a G-protein activator, were not altered following histamine pre-incubation. 2. The histamine H1-receptor (H1R) desensitization could be antagonized by mepyramine (an H1-receptor antagonist, 1 microM) but not by cimetidine (an H2-receptor antagonist, 10 microM), indicating that the desensitization occurred via stimulation of histamine H1-receptors, without evidence for the involvement of histamine H2-receptors. 3. Indomethacin (10 microM) did not block the H1R desensitization, suggesting no involvement of prostaglandins. Furthermore, histamine pre-incubation in calcium free medium still induced a functional uncoupling of H1R. 4. GF 109203X, a protein kinase C (PKC) inhibitor, and H-7, a non-selective kinase inhibitor, did not antagonize the homologous H1R desensitization. 5. The steady-state level of H1R mRNA, assessed by Northern blot analysis, was not affected by prolonged histamine exposure (100 microM, 0.5, 1, 2, 4, 16 and 24 h). 6. These results suggest that histamine induces desensitization of the H1R at the level of the receptor protein, which involves a mechanism independent of PKC, PKA, PKG and calcium influx, suggesting the involvement of a receptor-specific kinase.     

X-ray photoelectron spectroscopy of BSA and ethyl vinyl sulfone modified BSA

1. The 'fade' phenomenon seen in acid gastric secretion in response to a continuous intravenous infusion of pentagastrin has been studied in anaesthetized cats. Whereas acid secretion to a continuous infusion of histamine steadily increased for 3 hr, that to pentagastrin infusion rose steeply to a maximum at 45 min and then decreased gradually to reach about 60% of maximum after 2 hr. 2. Pre-treatment of the cats with the 5-hydroxytryptamine (5-HT) blocking drugs, methysergide and cyproheptadine or with the 5-hydroxytryptamine-depleting drug reserpine completely altered the pattern of secretion to pentagastrin such that the response was similar to that seen during an infusion of histamine. These drugs did not affect secretion stimulated by histamine. 3. It is suggested from these results that pentagastrin releases 5-hydroxytryptamine which at first potentiates and then inhibits the resulting stimulated secretion.     

Developmental regulation of gastric somatostatin secretion in the sheep

Gastric somatostatin (SRIF) regulates gastric acidity by inhibiting gastric acid and gastrin secretion. SRIF secretion is increased by gastric acidity and also directly by regulators of gastric acid secretion such as gastrin. This direct effect has not been described in the developing animal, nor have the roles of intermediaries such as histamine and gastric acidity been defined. The present study aimed to establish the regulatory role of gastrin and histamine during development on SRIF secretion and also to determine whether the effects of gastrin and histamine are independent of gastric pH. Pentagastrin and histamine were infused on separate occasions into fetal sheep, newborn lambs, and 28-day-old lambs. To determine the roles of endogenous histamine and gastric pH, ranitidine (a histamine-2 receptor antagonist) and omeprazole (a H+/K+ ATPase inhibitor) were coinfused with the agonists. Plasma SRIF and gastrin concentrations were measured by RIA. Pentagastrin stimulated SRIF secretion in the fetus after 131 days of gestation (term is 147 days), whereas stimulation by histamine was effective only after birth. The SRIF stimulatory effect of pentagastrin in 28-day-old lambs was abolished by ranitidine, which also reduced this effect in the adult sheep. This inhibitory effect of ranitidine was shown to be a result of blockade of stimulatory H2 receptors, because in the adult blockade of acid secretion with omeprazole failed to attenuate the response of histamine. These results indicate that in the fetus, gastrin receptors, but not histamine receptors, are functionally involved in the stimulation of SRIF secretion. After birth, both gastrin and histamine stimulate SRIF, but the effect of gastrin is mediated at least in part by the release of endogenous histamine. These responses occur independently of changes in gastric acidity, supporting the concept of a direct negative feedback between SRIF and gastrin.     

Effect of histamine on canine gastric mucosal adenylate cyclase

The effects of histamine, Nalpha-dimethylhistamine, 4,5-methylhistamine, Ntau-methylhistamine, pentagastrin, carbachol, and NaF on the adenylate cyclase activity from canine gastric mucosa were investigated in cell-free preparations. In gastric fundic mucosa, histamine (10(-4) M), Nalpha-dimethylhistamine (10(-4) M), 4,5-methylhistamine (10(-4 M), and NaF (10)-2) M) significantly (P less than 0.001) increased adenylate cyclase activity (means+/-SE) by 44.7+/-6.6, 49.4+/-6.7, 34.0+/-6.4, and 572.0+/-100%, respectively, above basal activity. The effect of histamine and Na-dimethyl histamine was dose-dependent. In contrast, other tested agents failed to stimulate the formation of cyclic AMP in gastric fundic mucosa. Metiamide (10(-4) M) blocked the stimulation of fundic mucosa adenylate cyclase by histamine and Nalpha-dimethylhistamine, without significantly altering basal and NaF-induced adenylate cyclase activity. Histamine, however, did not stimulate the adenylate cyclase activity from the gastric antral mucosa. The findings support the proposal that the canine gastric acid response to histamine may be mediated by cyclic AMP formed in response to stimulation of histamine H2-receptors.     

Direct evidence for histamine H3 receptor-mediated inhibition of norepinephrine release from sympathetic terminals of guinea pig myocardium

AIM: To study the histamine H3 receptors mediated inhibition of norepinephrine (NE) release from cardiac sympathetic terminals of guinea pig isolated atria. METHODS: Release of NE induced by electric field stimulation (50 mA, 5 ms) in the bath solution was measured by HPLC-ECD. RESULTS: The release of NE caused by field stimulation was attenuated by (R)-alpha-methyl-histamine (alpha-MeHA, 0.1 nmol.L-1(-10) mumol.L-1) in a concentration-dependent manner. Thioperamide concentration-dependently antagonized the inhibition of alpha-MeHA. Blockade of H1, H2, alpha 2, beta 2-receptors failed to prevent the inhibitory effect of alpha-MeHA. Thioperamide (1 nmol.L-1(-10) mumol.L-1), when used alone, concentration-dependently facilitated the release of NE evoked by field stimulation. CONCLUSION: The presynaptic histamine H3-receptors inhibited the NE release from cardiac sympathetic terminals.     

The gastric antisecretory activity of a phenothiazine molecule, LM 24056

The effect on the gastric secretion of the phenothiazine molecule N,N-dimethyl-10-(3-quinuclidinyl)-2-phenothiazine sulfonamide (LM24056) was studied in dogs equipped with gastric fistula and denervated pouch. The gastric stimulation was obtained either by exogenous stimulants (gastrin, gastrin + bethanechol, histamine) or by endogenous ones released by feeding gastrin; LM 24056 was infused i.v. 1. I.v. administration of 1.25 to 5 mg . kg-1 . h-1 of LM 24056 had a nearly complete inhibitory action on gastric juice secretion (acid and pepsin), on gastrin- and gastrin + bethanechol-stimulated secretion. The LM, 24056 concentration which produced 50% inhibition (IC50%) of acid and pepsin secretion was about 1.25 mg . kg-1 . h-1. 2. LM 24056 appeared to be unable to reduce the histamine-stimulated secretion. 3. I.v. administration of 1 to 30 mg . h-1 of LM 24056 reduced or abolished both gastric acid secretion and gastrin release. The IC50 was 5 mg . h-1 (or about 0.5 mg . kg-1 . h-1) for both responses. The possible mechanism of action of LM 24056 is discussed in comparison with those of H2-receptor antagonists, of atropine and of pirenzepine, respectively.     

Objective assessment of photoreceptor displacement and metamorphopsia: a study of macular holes

OBJECTIVE: To determine gastric secretory responses in horses treated with histamine and to determine the dose of histamine needed to elicit maximal gastric secretion. ANIMALS: 6 adult horses with an indwelling gastric cannula. PROCEDURE: Gastric contents were collected in 15-minute periods, and volume, pH, hydrogen ion concentration, hydrogen ion output, sodium concentration, and sodium output were determined. Values were determined without any treatment (baseline), after administration of pyrilamine maleate (1 mg/kg of body weight, i.v., given during a 15-minute period), and during 1-hour infusions of histamine at 3 rates (7.5, 15, and 30 microg/kg/h, i.v.). RESULTS: Volume and hydrogen ion concentration of gastric contents and hydrogen ion output were significantly increased, compared with baseline values, during histamine infusion. Mean hydrogen ion concentration and hydrogen ion output were significantly greater during infusion of histamine at a rate of 15 or 30 microg/kg/h than at a rate of 7.5 microg/kg/h. Sodium concentration was significantly decreased, compared with baseline value, during histamine infusion, but sodium output was unchanged. CONCLUSIONS: Histamine at doses of 15 and 30 microg/kg/h, i.v. stimulated maximal gastric secretion in horses. Histamine appeared to induce only parietal secretion. CLINICAL RELEVANCE: This study provides additional information related to equine gastric physiology, which may benefit further understanding of the pathogenesis of peptic ulcer disease.