Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The actions of two mast cell stabilising agents, FPL 52694 and disodium cromoglycate and the Ca2+ channel antagonist verapamil on acid secretion by the rat isolated stomach have been studied. FPL 52694 (1-5 mM) in the serosal medium stimulated acid secretion. This was antagonised by prostaglandin E2 but not by atropine, metiamide, propranolol or tetrodotoxin. FPL 52694 (1-5 mM) in the mucosal medium had an inhibitory effect on basal acid secretion and that stimulated by pentagastrin and histamine. The inhibition reversed only slowly after removal of FPL 52694. Disodium cromoglycate and serosal application of verapamil had no significant effects on acid output. Removal of calcium from the bathing solutions and mucosal verapamil inhibited basal secretion. Topically applied, FPL 52694 is a potent inhibitor of acid secretion in vitro. This effect may involve an action upon the availability of calcium to the tissue. The stimulatory effects of serosal FPL 52694 are discussed in relation to previous in vivo findings.
 ...
PMID:The action of two mast cell stabilising agents and verapamil on rat gastric acid secretion in vitro. 393 83

A single intraperitoneal injection of compound 48/80 (48/80) (0.5-3 mg/kg) into anesthetized rats caused a dose-dependent reduction of the transmucosal potential difference (PD) and intraluminal pH (pH), and induced gastric lesions within 2 h. These same changes were seen with an intraperitoneal injection of histamine, but not with serotonin. There was a significant correlation between the lesion index and the PD reduction, although the integrity of the resting gastric mucosal barrier remained unaltered. The PD reduction caused by 48/80 was dose-dependently inhibited by tripelennamine (H1-antagonist) and FPL-52694 (mast cell stabilizer) and partially suppressed by methysergide (serotonin antagonist), but the changes in pH were prevented by FPL-52694 and cimetidine (H2-antagonist). The reduction of PD and pH induced by histamine was inhibited by tripelennamine or cimetidine, respectively, but these responses were not inhibited by FPL-52694 or methysergide. Gastric lesions induced by 48/80 were potently inhibited by tripelennamine and FPL-52694, and partially by cimetidine, whereas those induced by histamine were significantly prevented by tripelennamine and cimetidine, but not by FPL-52694. Methysergide had no effect on the development of gastric lesions in response to 48/80 or histamine. These results suggest that a single injection of 48/80 reduced the PD and stimulated acid secretion, thereby producing gastric lesions. These effects of 48/80 may be due to activation of H1- and H2-receptors by acutely released endogenous histamine.
 ...
PMID:Mechanisms of irritative activity of compound 48/80 on rat gastric mucosa. 394 Feb 36

Intraperitoneal administration of 0.75 mg/kg of compound 48/80 (a mast cell degranulator) once daily for four days induced extensive gastric lesions in rats. Oral administration of tripelennamine (histamine H1-receptor antagonist) and cimetidine (histamine H2-receptor antagonist) twice daily for four days had little or no effect on the lesion formation. Oral administration of methysergide and cyproheptadine (serotonin antagonists) and FPL-52694 (a mast cell stabilizer) potently inhibited the compound 48/80-induced lesions. Intraperitoneal administration of histamine plus serotonin, or serotonin alone, induced gastric lesions which resembled those induced by compound 48/80. These lesions were potently inhibited by methysergide and cyproheptadine, but not by tripelennamine, cimetidine, and FPL-52694. Single or repeated administration of compound 48/80 significantly increased serum histamine and serotonin levels. After a single administration of compound 48/80, the increased histamine levels rapidly returned to normal levels, but serotonin levels remained high for 7 hr. Histamine and serotonin levels in the gastric mucosa were transiently increased after a single administration of compound 48/80, but remained normal after repeated administration. Single or repeated administration of compound 48/80 had little effect on arterial blood pressure. The compound 48/80-induced gastric lesions appear to be caused primarily by the release of serotonin, but not histamine, from extragastric sources.
 ...
PMID:Pathogenesis of compound 48/80-induced gastric lesions in rats. 395 35

The effects of a new monochrome mast cell stabilizer (FPL 52694) on gastric secretion have been studied in healthy volunteers. When administered orally for 3 days, FPL 52694 consistently reduced nocturnal and pentagastrin-stimulated secretion of acid by about 50%. Meal-stimulated gastric secretion was not affected by the drug. Inhibition of the gastric secretory response to pentagastrin was not significant when single doses of the drug were administered either into the stomach or the duodenum, but administration of multiple doses resulted in significant inhibition. The drug does not inhibit gastric secretion by injuring the gastric mucosa, since the gastric mucosal barrier to back diffusion of hydrogen ions is not affected. We conclude that this mast cell stabilizer provides an interesting tool for studying aspects of the physiological control of gastric secretion and may have a therapeutic role in peptic ulceration.
 ...
PMID:Effects of a mast cell stabiliser (FPL 52694) on human gastric secretion. 407 27

Allergic sheep respond to inhalation challenge with Ascaris suum antigen with an immediate bronchoconstriction that resolves within 2 to 4 h, followed by a second bronchial obstruction occurring 6.5 to 8 h after challenge. The purpose of this study was to determine if the antigen-induced late bronchial response in allergic sheep is mediator dependent and to determine the extent to which histamine and/or slow-reacting substance of anaphylaxis (SRS-A) are involved in this response. To do this, 10 conscious sheep with Ascaris suum hypersensitivity underwent an inhalation challenge with antigen, and the average increase in specific lung resistance (SRL = mean pulmonary flow resistance times thoracic gas volume) was determined for each animal between 6.5 and 8 h after challenge, i.e., the time of late bronchial response. On another occasion, separated by at least 14 days, the animals were rechallenged with antigen, but prior to the onset of the late response (5.5 h) the animals were treated with either the mast cell stabilizer cromolyn (1 mg/kg), the SRS-A antagonist FPL-55712 (3 ml of a 1% wt/vol solution), or the histamine H1. receptor antagonist chlorpheniramine (2 mg/kg). Compared with the control response, inhaled aerosols of cromolyn or FPL-55712 blocked the late increase in SRL (p less than 0.01). Intravenously administered chlorpheniramine alone, or in conjunction with atropine, had no effect on the late response. Finally, the late response was partially reversed by FPL-55712 inhalation. These results suggest that the late bronchial response after inhalation challenge in allergic sheep is mediator dependent, and that SRS-A is a principal mediator of this response.
 ...
PMID:The role of slow-reacting substance of anaphylaxis in the late bronchial response after antigen challenge in allergic sheep. 620 32

Immunologic degranulation of airway mast cells after antigen inhalation produces early and late airway obstructions in allergic sheep. In this study we determined whether nonimmunologic degranulation of airway mast cells by inhalation of compound 48/80 had similar effects. In five sheep, pulmonary flow resistance (RL), thoracic gas volume (Vtg), and arterial O2 tension (Pao2) were determined prior to and at predetermined times after inhalation of 48/80 aerosol. Immediately after challenge mean specific lung resistance (sRL = RL X Vtg) increased by 259% and mean Pao2 decreased by 29%. All values returned to normal by 3 h. By 5-h postchallenge sRL again increased significantly; this second increase in sRL (92% above base line) was maximal at 7 h and was accompanied by a 17% drop in Pao2. In these same sheep inhalation of Ascaris suum antigen produced comparable early changes in sRL, but the onset of the late response was somewhat delayed and more pronounced. In a second group of sheep (n = 5), pretreatment with the mast cell stabilizer cromolyn sodium prevented both early and late responses by compound 48/80. Pretreatment with the histamine H1-antagonist chlorpheniramine had no significant effect on either response, whereas pretreatment with FPL 55712, an antagonist of slow-reacting substance of anaphylaxis (SRS-A), slightly but not significantly attenuated the early response and completely prevented the late response. We conclude that, like immunologic stimuli, nonimmunologic mast cell degranulation produces early and late bronchial obstructions in allergic sheep; that these responses are mediator dependent; and that while histamine and SRS-A contribute to the early response, it is the early appearance of SRS-A which is an important prerequisite for the late response.
 ...
PMID:Late phase bronchial obstruction following nonimmunologic mast cell degranulation. 620 56

Studies have been made of the electrolyte output in the gastric juice of conscious dogs equipped with gastric fistulae during stimulation by intravenous infusion of either pentagastrin (2 micrograms kg-1 h-1), histamine (30 micrograms kg-1 h-1) or insulin (0.1 u kg-1 h-1). The mast cell stabilizing agent, FPL 52694 (4.35 mg ml-1) was instilled into the stomach for 30 min and caused a marked reduction of H+ output, H+ concentration and osmotic strength of the juice during stimulation with pentagastrin, histamine, or insulin. There was also a marked increase in the rate of Na+ output into the juice. When pentagastrin-stimulated acid secretion was inhibited by cimetidine (4 mumol kg-1 i.v.) acid output was reduced but there were no sustained changes in ion concentrations, osmolarity or Na+ output of the type seen following inhibition with FPL 52694. It is concluded that FPL 52694 may have a dual mode of action in this preparation; a direct reduction of the output of hydrochloric acid and a smaller effect to increase gastric NaHCO3 output leading to a post-secretory neutralization of the juice.
 ...
PMID:Gastric juice electrolyte secretion in conscious dogs with gastric fistulae and its modification by FPL 52694, a mast cell stabilizing agent. 635 36

We have previously established a relationship between mast cell degranulation and hypoxic pulmonary vasoconstriction (HPV). In the present study, we investigated the possible role of slow-reacting substance of anaphylaxis (SRS-A) in the mediation of HPV. In 18 conscious sheep, pulmonary artery pressure, pulmonary arterial wedge pressure, and cardiac output were measured for the calculation of pulmonary vascular resistance (PVR) along with arterial oxygen tension (PaO2) while breathing room air and while breathing 13% O2 (balance, N2). Before and during 13% O2 breathing (pretreatment), Group 1 received an intravenous infusion of cromolyn sodium (3 mg/kg-1/min-1) and Group 2 was infused with FPL-57231, a SRS-A antagonist (2 mg/kg-1/min-1); Groups 3 and 4 received infusions of cromolyn sodium or FPL-57231 after induction of HPV. During 13% O2 breathing (mean PaO2, 47 mmHg), mean PVR increased to 190% of baseline. Pretreatment with cromolyn sodium prevented HPV, whereas infusion of cromolyn sodium after induction of HPV failed to reverse it; FPL-57231 both prevented HPV (pretreatment) and reversed it when infused after induction of HPV. Pretreatment with the prostaglandin synthetase inhibitor indomethacin (2 mg/kg) 1 h before the experiment failed to modify the FPL-57231-induced reversal of hypoxic vasoconstriction, thus excluding the release of inhibitory prostaglandins by this compound. We conclude that cromolyn sodium prevented HPV, presumably by inhibiting the release of SRS-A, which mediates pulmonary vasoconstriction directly or indirectly through other mechanisms.
 ...
PMID:Does slow-reacting substance of anaphylaxis mediate hypoxic pulmonary vasoconstriction? 640 64

Rats treated with chronic hypobaric hypoxia (21 days, 380 Torr) and mast cell stabilizing compound FPL 55618 had significantly less right ventricular hypertrophy and lung mast cell hyperplasia than rats subjected to chronic hypoxia alone. Right ventricular blood pressure was not reduced.
 ...
PMID:Mast cell stabilizing compound FPL 55618 reduces right ventricular hypertrophy and lung mast cell hyperplasia in chronically hypoxic rats. 645 49

In a double blind crossover experiment in 16 healthy male volunteers, the effects of oral FPL 52694 and a matching placebo upon pentagastrin stimulated gastric acid secretion, gastric mucosal histamine content, and gastric mucosal mast cell count were compared. There was a significant increase in acid secretion, and a fall in tissue histamine and the mast cell count after treatment with the placebo. All these changes were inhibited by FPL 52694, and there was a significant difference between the effects of this compound and the placebo in all three parameters. It is concluded that FPL 52694 caused significant inhibition of acid secretion, and that the likely mechanism of action is by stabilisation of mast cells and inhibition of histamine release.
 ...
PMID:Action of FPL 52694 on gastric acid secretion in the healthy human stomach. 650 Mar 62


<< Previous 1 2 3 4 5 Next >>