British journal of pharmacology
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1. A technique is described for obtaining a myometrial preparation devoid of endometrium, from the uterus of the rat in oestrus. 2. Acetylcholine and prostaglandin F2alpha (PGF2alpha) produced concentration-effect curves with the same maximal tensions and slope on the whole uterus and myometrial preparations. ⋯ This significant enhancing effect of PGF2alpha was only seen with the threshold dose of acetylcholine. 5. It appears that the mechanism of action of bradykinin and oxytocin on the rat uterus involves both a direct action and an indirect action. The indirect action possibly involves release of prostaglandin(s) from the endometrium.
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1 The nature of the catecholamine-induced contracture of chronically denervated mouse diaphragm muscle has been investigated and compared with the contractural response evoked by acetylcholine. 2 The time course of onset of catecholamine-sensitivity in denervated diaphragm muscles was similar to the development of acetylcholine sensitivity. However, catecholamine contractures were absent in tissues denervated for periods longer than 90 days whereas acetylcholine-sensitivity was still evident several months after denervation. 3 The catecholamine-induced contracture of the denervated muscle was inhibited specifically by beta-receptor blocking drugs and was unaffected by alpha-receptor blocking drugs and cholinoceptor antagonists. 4 Catecholamine-induced contractures of denervated muscles, unlike contractures to acetylcholine, were dependent upon the presence of spontaneous fibrillation and the amplitude of spontaneous fibrillation was increased by catecholamines. ⋯ Under these conditions catecholamine-induced contractures, but not those to acetylcholine, were abolished. 5 Labelled calcium was found progressively to enter denervated muscle fibres and this entry of calcium was increased by catecholamines. It is suggested that this calcium entry may represent either an increased calcium permeability of denervated muscle fibres which is increased further by catecholamines or the presence of a calcium current that occurs during the fibrillatory potentials of denervated muscle.
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1 During the first 90 min following oral administration of sulphacetamide, there was a rapid decline in plasma drug concentration in control mice whereas a progressive increase in sulphacetamide concentration was observed in leukaemic mice. 2 Similar changes in the kinetics of sulphacetamide distribution were observed in the liver, spleen and muscle. 3 While the concentration of sulphacetamide remained quite constant in the brain and fat tissue of control mice, a progressive increase in drug concentration was observed in the brain and fat tissue of leukaemic mice. 4 Some of these changes in the kinetics of sulphacetamide tissue distribution are compatible with delay in gastrointestinal absorption of the drug and its accumulation in the ascitic fluid.
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1 The elimination kinetics of [(14)C]-neostigmine iodide and [(14)C]-3-hydroxyphenyltrimethyl-ammonium iodide (3-OH PTMA) have been studied in the rat.2 The presence of a renal secretory pathway for neostigmine and 3-OH PTMA has been confirmed.3 For neostigmine and 3-OH PTMA, at a given dose level, the fraction of the dose eliminated unchanged was reduced and the metabolite fraction was increased after portal vein administration when compared to jugular vein administration. This indicates that both compounds are subject to extensive metabolism during the first passage through the liver.4 Neostigmine was eliminated by dose-independent kinetics after jugular vein administration but dose-dependent after portal vein administration. ⋯ This increase was not accompanied by any change in the fraction of the metabolites eliminated.5 After portal vein administration of 3-OH PTMA, the fraction of the dose eliminated as 3-OH PTMA also increased with increasing dose. This change was accompanied by a decrease in the fraction of the metabolites eliminated which were excreted at a constant rate.
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Role of inorganic nitrite in methaemoglobin formation after nitrate ester administration to the rat.
1. Methaemoglobin is rapidly formed during the incubation of rat red cells with inorganic nitrite, whereas ethylene glycol dinitrate at a higher concentration has little effect.2. ⋯ The methaemoglobin formed after ethylene glycol dinitrate or glyceryl trinitrate injection is equivalent to that produced from nitrite infusions simulating its formation from the nitrate esters.3. It is concluded that methaemoglobin arising from nitrate ester administration is formed principally by the action of the metabolite inorganic nitrite.