Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ca dependence of contraction and myosin phosphorylation was investigated in canine tracheal smooth muscle stimulated with carbachol, K or serotonin. Previous studies of tracheal muscle showed carbachol concentration-response curves for contraction and myosin phosphorylation were superposable. In contrast, there was a striking difference in the Ca++ sensitivities of tension and myosin phosphorylation when Ca++ concentration-response curves were constructed in the presence of 10(-7) M carbachol. Significant phosphorylation (greater than 0.3 moles phosphate/mole 20,000 dalton myosin light chain) was observed in the absence of active tension. In the present study, carbachol (10(-7) and 10(-6) M) and serotonin (10(-5) M) also induced significant myosin phosphorylation in low Ca++ solutions (0-0.025 mM CaCl2) without proportional increases in tension. K+ depolarization in Ca++-free physiological salt solution (60 mM KCl, 10(-6) M atropine) yielded phosphorylation not significantly different from basal levels. All stimulants induced active stress after readmission of Ca. The Ca++ dependence curve for myosin phosphorylation in muscles stimulated with carbachol was shifted up and to the left of the force curve. Atropine (10(-6) M) significantly reduced phosphorylation induced by carbachol in Ca++-free solutions, as did 3 X 10(-6) M nifedipine and 10 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Phorbol 12-myristate, 13-acetate or phorbol 12,13-dibutyrate did not increase basal phosphorylation or phosphorylation in low Ca++ solutions, suggesting that protein kinase C did not phosphorylate myosin in this case. Myosin phosphorylation under these conditions is not sufficient to support contraction, and is reduced by treatments that decrease Ca++ entry.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dissociation of myosin phosphorylation and active tension during muscarinic stimulation of tracheal smooth muscle. 310 Jul 73

The mammalian small intestine is extensively innervated by cholinergic nerve fibers, including projections to the muscular and submucosal layers. This study tested the hypothesis that cholinergic agents modulate ileal transport independent of alterations in intestinal vascular resistance and motility. Ten-centimeter segments of rabbit ileum (n = 32) were vascularly perfused ex vivo with a physiologic electrolyte solution containing red cells. The lumen was perfused with an electrolyte solution containing [14C]polyethylene glycol. Net fluxes of water, sodium, and chloride were calculated during three 20-min periods: basal, drug infusion, and recovery. Agents infused at a final arterial concentration of 10(-5) mole/liter included acetylcholine, atropine, and hexamethonium. Measured perfusion pressure reflected changes in vascular resistance. Recovery calculations controlled for motility effects. Acetylcholine caused significant secretion of water, sodium, and chloride (P < 0.05). The infusion of atropine or hexamethonium alone had no effect. Atropine but not hexamethonium prevented the prosecretory effect of acetylcholine. There were no significant changes in perfusion pressure or 14C recovery for any infused agent. Acetylcholine-induced ileal secretion is (1) mediated via atropine-sensitive muscarinic cholinergic receptors, (2) independent of extraintestinal neural pathways, and (3) independent of changes in vascular resistance or motility. These data support the hypothesis that acetylcholine influences ileal transport directly, independent of alterations in vascular resistance and motility.
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PMID:Cholinergic agents modulate transport in the isolated, perfused ileum. 853 65

The effect of 18 pyridinium aldoximes on diethylphosphoryl-acetocholinesterase in vitro and the protection against lethal poisoning by ethyl pyrophosphate (TEPP) in mice pretreated with 0.095 m.mole/kg. of these oximes was investigated. Monoximes and dioximes of polymethylenebispyridinium compounds were studied in greater detail since they were up to 22 times more potent than pyridine-2-aldoxime methiodide (2-hydroxyiminomethyl-N-methylpyridinium iodide) in reactivating diethylphosphoryl-acetocholinesterase in vitro and protected mice against lethal poisoning by up to 15 LD100 of ethyl pyrophosphate. These oximes were also up to 52 times more potent than pyridine-2-aldoxime methiodide in reactivating di-isopropylphosphoryl-acetocholinesterase in vitro and were effective in preventing lethal poisoning by dyflos (di-isopropyl phosphorofluoridate). The antidotal action against diethyl phosphostigmine (Ro 3-0340) was even greater than that against ethyl pyrophosphate. Some of the most effective oximes had antidotal actions in poisoning by ethyl pyrophosphate, diethyl phosphostigmine and dyflos when given in 0.0095 m.mole/kg. and this effect was enhanced by 1 mg./kg. atropine sulphate. In vivo reactivation of diethylphosphoryl-acetocholinesterases by 0.0095 or 0.095 m.mole/kg. of oximes of polymethylenebispyridinium compounds was demonstrated in blood but not in brain. Atropine-like and neuromuscular blocking activities were studied on isolated organs and protection against lethal doses of neostigmine and related anticholinesterases were also investigated. Some of the oximes of polymethylenebispyridinium compounds have, relative to pyridine-2-aldoxime methiodide, a higher therapeutic ratio in mice and considerably greater water-solubility. The possible advantages to be gained from their use in preference to pyridine-2-aldoxime methiodide are discussed.
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PMID:Protection against lethal organophosphate poisoning by quaternary pyridine aldoximes. 1366 73

Dissociation constants and corresponding pK(a) values of five drugs were obtained with the Bates-Schwarzenbach method using a Perkin-Elmer Lambda 35 UV/vis spectrophotometer at temperature 298.15 K in the buffer solutions. Atropine, promethazine hydrochloride, ibuprofen, flurbiprofen, and meclofenamic acid sodium salt exhibited pK(a) values of 10.3, 6.47, 5.38, 4.50, and 4.39, respectively. The equilibrium mole fraction solubilities of six drugs were measured in a range of temperatures from 240 to 340 K in three important solvents for drugs: water, ethanol, and 1-octanol using the dynamic method. The basic thermal properties of pure drugs, i.e., melting and glass-transition temperatures, as well as the enthalpy of melting and the molar heat capacity at glass transition (at constant pressure) have been measured with the differential scanning microcalorimetry technique (DSC). Molar volumes have been calculated with the Barton group contribution method. The experimental solubility data have been correlated by means of three commonly known G(E) equations: the Wilson, NRTL, and UNIQUAC, with the assumption that the systems studied here have revealed simple eutectic mixtures. As a measure of goodness of correlation, the root-mean-square deviations of temperature have been used. The activity coefficients of the drugs in saturated solutions for each correlated binary mixture were calculated from the experimental data.
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PMID:pKa and solubility of drugs in water, ethanol, and 1-octanol. 1951 53