Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Goat isolated trachea contracted in response to carbachol, histamine and 2-pyridylethylamine (an H(1)-receptor agonist) and relaxed after application of isoprenaline. 5-hydroxytryptamine (5-HT) and phenylephrine.2 Mepyramine, a selective H(1)-receptor antagonist, blocked histamine- and 2-pyridylethylamine-induced contractions. In high doses it also exhibited some nonspecific antagonism to carbachol. After H(1)-receptor blockade, 4-methylhistamine and dimaprit (specific H(2)-agonists) relaxed the carbachol-contracted trachea.3 Propranolol, a beta-adrenoceptor blocker, antagonized relaxation in response to isoprenaline and phenylephrine. In high doses, it produced a reversal of the phenylephrine response.4 Indomethacin enhanced contractions in response to carbachol and histamine.5 Relaxation to 5-HT was not affected by propranolol, indomethacin, metiamide or cimetidine (H(2)-blockers). These findings appear to exclude the involvement of adrenergic, prostaglandinergic and H(2)-histaminergic mechanisms in the mediation of this response.6 Atropine potentiated 5-HT-induced relaxations. This suggests the participation of a ;masked' excitatory cholinergic mechanism.7 Methysergide, dibenamine and dibenzyline selectively antagonized or reversed 5-HT-induced relaxation. Dibenamine and dibenzyline enhanced relaxations to isoprenaline.8 This investigation showed (i) a relaxant response of goat trachea to 5-HT, mediated via D-muscular tryptamine receptors; (ii) a small population of excitatory M-neuronal tryptamine and alpha-adrenoceptors; and (iii) predominance of H(1)-histamine receptors in the goat trachea.
 ...
PMID:Relaxant response of goat trachea to 5-hydroxy-tryptamine mediated by D-tryptamine receptors. 46 88

The allergic bronchoconstriction in guinea pigs has been attributed mainly to the release of mast cell mediators. Histamine has been involved in the first minutes of the anaphylactic reaction and new-formed compounds in the subsequent response. In this asthma model the vagal influence has been sparsely investigated. In the present work we evaluated the pharmacological modification of the acute allergic bronchoconstrictor response in guinea pigs sensitized to ovalbumin through aerosol exposure. Pyrilamine (20 micrograms/kg), diethylcarbamazine (a lipoxygenase inhibitor, 10 mg/kg) and dexamethasone (4 mg/kg) each reduced the antigen-induced bronchoconstriction throughout the 30 min studied. Indomethacin (3.1 mg/kg) did not modify the response to the antigen. Atropine (2 mg/kg) plus bilateral vagotomy also diminished this response from 5 min onward. On the other hand, from 5 min ahead pyrilamine-resistant bronchoconstriction was partially inhibited by dexamethasone, and it was almost completely blocked during all of the response when atropine plus bilateral vagotomy were added to dexamethasone. Dipyridamole (an inhibitor of the adenosine uptake, 0.4 mg/kg) enhanced the bronchoconstriction, though this was significant only in the 2-5 min time-interval of the response. These results suggest that histamine and vagal influence play an important role in the whole response to antigen, that other mediators, probably leukotrienes, participate in this response from 5 min onward, and that adenosine could exert a potentiation effect on this response.
 ...
PMID:Pharmacological characterization of mediators and vagal influence in the acute allergic bronchoconstriction in guinea pigs. 228 Jul 95

Exposure of conscious guinea pigs to A23187 aerosol produced a concentration-related increase of excised lung gas volumes (ELGV), i.e., postmortem pulmonary gas trapping. Measurements of ELGV were highly correlated with in vivo measurements of dynamic compliance (Cdyn) and total pulmonary resistance (RL) and were used as an indication of in vivo airway obstruction. We pretreated guinea pigs intravenously with the following drugs: atropine; LY163443, a selective LTD4/E4 antagonist; indomethacin; propranolol; and pyrilamine. The guinea pigs were exposed for 8 minutes to the A23187 aerosol, and ELGV measurements were then made. Atropine or pyrilamine prevented the A23187-induced gas trapping. Indomethacin or propranolol tended to potentiate the response and when combined, they potentiated the gas trapping by 80%. LY163443 had no effect alone, but when combined with indomethacin, propranolol, and pyrilamine, inhibited A23187-induced gas trapping by 67%. We conclude that cholinergic and histaminergic mechanisms play major roles in the ionophore-induced pulmonary gas trapping of the guinea pig. With appropriate pretreatment, sulfidopeptide leukotrienes may produce a substantial effect.
 ...
PMID:Mechanism of A23187-induced airway obstruction in the guinea pig. 244 75

1. The effect of transection of pudendal or hypogastric nerves and of various pharmacological pretreatments on the bladder voiding cycle elicited by saline filling was investigated in urethane-anesthetized rats. 2. Sectioning of pudendal nerves reduced efficiency of the expulsive phase of the voiding cycle while sectioning of hypogastric nerves enhanced voiding efficiency and reduced residual volume. 3. An increased voiding efficiency was also observed in 6-hydroxydopamine-treated rats. 4. Atropine and physostigmine decreased and increased voiding efficiency, respectively. Indomethacin pretreatment produced a marked increase in residual volume. 5. These findings indicate that the autonomic innervation of the bladder and urethra as well as production of local factors such as prostanoids regulates not only the collecting phase of the cystometragram but also influence markedly voiding efficiency.
 ...
PMID:Further studies on mechanisms regulating the voiding cycle of the rat urinary bladder. 251 94

Antigen challenge of jejunal epithelium from rats sensitized to egg albumin induces an active Cl- secretory process secondary to release of mucosal mast cell mediators. The present study was designed to define the relative role of these mast cell mediators and the enteric nervous system in the transport abnormalities associated with intestinal anaphylaxis. Net ion transport of stripped jejunal tissue from sensitized and sham-treated animals was studied in Ussing chambers. The Cl- secretory response induced by egg albumin during intestinal anaphylaxis was similar to that after addition of 5-hydroxytryptamine (5-HT), histamine, and prostaglandins D2 and E2 to jejunal tissue. Cinanserin, a 5-HT2-receptor antagonist, virtually abolished the response to 5-HT and totally abolished the response to egg albumin. Methysergide, a 5-HT1-receptor antagonist had no effect on either response. Indomethacin, an inhibitor of prostaglandin synthesis, significantly inhibited the 5-HT and egg albumin response. Diphenhydramine, an H1-receptor antagonist and cimetidine, an H2-receptor antagonist both significantly inhibited the histamine response but neither altered the response to egg albumin. Atropine, an anticholinergic, and tetrodotoxin, a nerve blocker, did not inhibit the antigen induced anaphylactic response. These results indicate that 5-HT, acting through 5-HT2 receptors is largely responsible for the transport abnormalities seen in intestinal anaphylaxis induced by egg albumin while prostaglandins appear to play a partial role. The findings do not support a role for the enteric nervous system for the egg albumin induced changes in Cl- secretion.
 ...
PMID:Intestinal anaphylaxis in the rat: mediators responsible for the ion transport abnormalities. 251 72

Alkaline secretion measured under basal conditions in the intact stomach of conscious dogs averaged 47 mumol/30 min and was about twice lower than that recorded in the proximal (approximately 7 cm long) portion of the duodenum. Vagal excitation elicited by sham feeding and insulin resulted in a marked stimulation of alkaline secretion both from the stomach and the duodenum. Atropine significantly reduced gastric and duodenal alkaline secretion under basal state. It abolished gastric and diminished duodenal alkaline response to sham feeding and insulin hypoglycemia, while propranolol was without significant influence. Indomethacin reduced by approximately 75% basal duodenal alkaline secretion but did not prevent the increment in alkaline response to vagal stimulation. We postulate the existence of the cephalic phase of gastroduodenal alkaline secretion, which seems to be cholinergically dependent in the stomach and partly of noncholinergic and nonadrenergic character but prostaglandin dependent in the duodenum.
 ...
PMID:Cephalic phase of gastroduodenal alkaline secretion. 303 38

Acetylcholine has been reported to produce vasodilation or vasoconstriction in the pulmonary circulation of different species. In rabbit lungs, acetylcholine is a potent vasoconstrictor. The present study was undertaken to examine the contractile effects of acetylcholine in arteries isolated from various regions of the rabbit pulmonary vascular bed and in thoracic aorta. Arteries isolated from within the lung were more responsive than extrapulmonary arteries (main pulmonary artery and aorta) to the contractile effects of acetylcholine. In vessels precontracted with norepinephrine, acetylcholine caused biphasic (relaxation-contraction) concentration-response curves. Atropine inhibited acetylcholine-induced contractions in all vessels, whereas pretreatment with cyclooxygenase or thromboxane synthetase inhibitors abolished contractile responses to acetylcholine only in intrapulmonary arteries. In accordance with these findings, acetylcholine caused a 3-fold increase in thromboxane A2 release from intrapulmonary arteries but not from extrapulmonary arteries. Inhibition of thromboxane synthetase abolished this effect of acetylcholine. Endothelium removal decreased contractile responses in intrapulmonary arteries but it did not decrease contractions in extrapulmonary arteries, suggesting that endothelium may contribute to acetylcholine-induced, thromboxane-mediated contractions in intrapulmonary arteries. Indomethacin did not inhibit contractile responses in endothelium-denuded main pulmonary artery or aorta but it abolished the weak contractile responses in intrapulmonary arteries without endothelium, indicating that arterial smooth muscle also was a source of contractile prostanoid biosynthesis enhanced by acetylcholine. These results demonstrate that acetylcholine contracts rabbit intrapulmonary arteries through generation of thromboxane A2 but that a different mechanism is responsible for mediating weaker acetylcholine-induced contractions in extrapulmonary artery and aorta.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Acetylcholine-induced contractions in isolated rabbit pulmonary arteries: role of thromboxane A2. 308 May 88

Bradykinin (BK; 10(-10)-10(-7) M) relaxes phenylephrine-contracted rabbit isolated pulmonary arterial rings. The mechanical destruction of the endothelial layer obliterates acetylcholine (ACh) and A23187-induced relaxation without influencing BK-, isoproterenol-, sodium nitroprusside- and papaverine-induced relaxations. Atropine and propranolol selectively antagonized ACh- and isoproterenol-induced relaxation, respectively, without influencing BK-induced relaxation. Indomethacin (1.4 X 10(-5) M, a potent cyclooxygenase inhibitor, 30-60 min) and p-bromophenacylbromide (5 X 10(-6) M, p-BPB, a potent phospholipase A2 inhibitor, 30-60 min) selectively inhibited BK-induced relaxation without influencing relaxation to isoproterenol, sodium nitroprusside and papaverine. These data suggest that BK stimulates PLA2 and releases arachidonic acid (AA), which is further metabolized via cyclooxygenase and prostaglandin synthetase to prostacyclin (PGI2), causing relaxation of rabbit pulmonary arterial segments. The inhibition of ACh- and A23187-induced relaxation by p-BPB, but not by indomethacin, suggest that initial activation of PLA2 causes the release of AA, which is subsequently metabolized to endothelial-derived relaxant factor (EDRF; lipid peroxides, ROOH, ROO-?).
 ...
PMID:Pharmacological modulation of bradykinin-, acetylcholine- and calcium ionophore A23187-induced relaxation of rabbit pulmonary arterial segments. 311 70

In anesthetized guinea-pigs previously sensitized to ovalbumin by intratracheal immunization, the intravenous administration of propranolol (3.1 mg/kg) produced an increase in the respiratory insufflation pressure induced by ovalbumin. Atropine (2 mg/kg), zolertine (1 mg/kg) and indomethacin (3.1 mg/kg) did not antagonize the propranolol-induced airway hyperreactivity. Indomethacin at higher dose (10 mg/kg) and BW755c (10 mg/kg) decreased the potentiation of the respiratory insufflation pressure to ovalbumin. Our results suggest that besides the beta-blockade, propranolol-induced bronchial hyperreactivity to ovalbumin in sensitized guinea-pigs could be mediated by leukotrienes.
 ...
PMID:Possible role of leukotrienes in propranolol-induced airway hyperreactivity in sensitized guinea-pigs. 312 44

The inhalation of platelet activating factor (PAF) produces bronchoconstriction in normal and asthmatic subjects. To identify the mechanism by which PAF-induced bronchoconstriction occurs in humans, bronchoprovocation testing was performed in 7 subjects (3 normal, 4 with mild asthma) after pretreatment with phosphate-buffered saline (PBS), atropine, chlorpheniramine, or indomethacin. We determined the nebulizer concentration of PAF which reduced specific airway conductance (SGaw) 35% (PC35 SGaw) and the slope of the PAF dose-response curve. Atropine produced baseline bronchodilatation (SGaw increased 50%), while chlorpheniramine and indomethacin had no effect on baseline pulmonary function. Atropine increased airway responsiveness to PAF: the PC35 SGaw decreased 40% (p less than 0.05) and the slope of the PAF dose-response curve increased 86% (p less than 0.05). In contrast, chlorpheniramine inhibited the airway response to PAF: the PC35 SGaw increased 87% (p less than 0.05), while the slope of the PAF dose-response curve decreased an insignificant 37%. Indomethacin did not affect either measurement. Chlorpheniramine also prevented the PAF-induced facial flushing and feeling of warmth; atropine and indomethacin did not. These results suggest that PAF-induced bronchoconstriction in humans is mediated at least in part by histamine release, not by cholinergic or cyclooxygenase-dependent mechanisms. Other indirect effects, such as the release of sulfidopeptide leukotrienes, or a direct effect on airway smooth muscle may also contribute to PAF-induced bronchoconstriction. Why atropine heightened the airway response to PAF is unclear.
 ...
PMID:Mechanism of platelet activating factor-induced bronchoconstriction in humans. 319


1 2 3 Next >>