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

The in vitro release of pepsinogen secretion by the isolated esophagus of the American bullfrog was studied with an improved model system. The tissue was mounted in a double chamber that preserves mucosal polarity and provides both control and test segments, each 1 cm2 from the same tissue. Pepsinogen secretion was severalfold higher than previously found with mucosal strips and could be sustained for several hours. Bethanechol (BCh) caused concentration-dependent (0.1-50 microM) pepsinogen secretion with a Vmax of 74 +/- 12 micrograms X mg prot-1 X h-1 or 50-60% of total pepsinogen; Km was 3 microM and 500 microM BCh stimulated at less than the Vmax value. Atropine specifically blocked BCh and pA2 = 9.3. In the presence of 100 microM isobutylmethyxanthine, BCh produced a dose-dependent increase in tissue cAMP but not cGMP. BCh remained effective in Ca2+-free medium. In calcium-free medium EGTA concentration dependently (0.2-5 mM) suppressed the pepsinogen response to BCh. The evidence thus far suggests that cholinergic stimulation of pepsinogen secretion in the tissue acts via both cAMP and Ca2+. More specific studies would be required for absolute confirmation of either or both apparent mechanisms and to resolve how they interact.
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PMID:Mediation of muscarinic stimulation of pepsinogen secretion in the frog. 257 56

The muscarinic receptors coupled to pepsinogen secretion on isolated frog esophageal peptic cells have been characterized using functional and radioligand binding techniques. N-[3H]methylscopolamine [( 3H]NMS) binding to intact cells was complex and indicative of a high affinity, low capacity site and a high capacity uptake site. Binding to the high capacity site was inhibited by atropine with high affinity (IC50, 3 nM) and by imipramine and propranolol with IC50 values of 70 and 270 nM, respectively. After inhibition of uptake by 30 microM propranolol, [3H]NMS bound to a single population of high affinity sites (KD, 125 +/- 16 pM), which exhibited binding site maximum of 2.1 fmol/10(6) cells, equivalent to 1260 sites/cell. Binding to these sites was reversible, stereoselective and inhibited by muscarinic receptor agonists with an order of potency: oxotremorine greater than acetylcholine greater than carbachol greater than bethanechol and by antagonists with an order of potency:atropine greater than 4-diphenylacetoxy-N-methylpiperidine methobromide greater than pirenzepine greater than AF-DX 116 (11-2[2-[[diethylamino) methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepine-6-one). Pepsinogen secretion was stimulated by the agonists with an order of potency: acetylcholine greater than or equal to carbachol greater than oxotremorine greater than bethanechol. Atropine, pirenzepine and AF-DX 116 competitively inhibited carbachol-stimulated pepsinogen secretion with pA2 values of 9.58, 7.37 and 6.68, respectively, which correlated with their log (inhibition constants) for receptor binding. By contrast, agonists with significant efficacy exhibited EC50 values which were 20 to 90 times lower than their inhibition constants for binding which suggests the possibility of "spare" muscarinic receptors. Our findings indicate that functional muscarinic receptors on peptic cells exhibit similar characteristics to the high affinity sites labeled by [3H]NMS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Muscarinic cholinergic receptor subtype on frog esophageal peptic cells: binding and secretion studies. 290 89