Steady-state kinetic analysis for the reaction of ammonium and alkylammonium ions with methylamine dehydrogenase from bacterium W3A1.
(49/87)
The steady-state kinetic mechanism for the reaction of n-alkylamines and phenazine ethosulfate (PES) or phenazine methosulfate (PMS) with methylamine dehydrogenase from bacterium W3A1 is found to be of the ping-pong type. This conclusion is based on the observations that 1/v versus 1/[methylamine] or 1/[butylamine] plots, at various constant concentrations of an oxidizing substrate, and 1/v versus 1/[PES] or 1/[PMS] plots, at various constant concentrations of a reducing substrate, are parallel. Additionally, the values of kcat/Km for four n-alkylamines are identical when PES is the oxidizing substrate, as were the kcat/Km values for four reoxidizing substrates when methylamine was the reducing substrate. Last, analysis of steady-state kinetic data obtained when methylamine and propylamine are presented to the enzyme simultaneously and PES and PMS are used simultaneously also supports the involvement of a ping-pong mechanism. The enzymic reaction with either methylamine or PES is dependent on the ionic strength, and the data indicate that each interacts with an anionic site on methylamine dehydrogenase. The presence of ammonium ion at low concentration activates the enzyme, but at high concentration this ion is a competitive inhibitor in the reaction involving methylamine and the enzyme. A complete steady-state mechanism describing these ammonia effects is presented and is discussed in light of the nature of the pyrroloquinoline quinone cofactor covalently bound to the enzyme. (+info)
A calcium blocking and anticholinergic agent (terodiline) in the treatment of detrusor hyperreflexia: a placebo-controlled, cross-over trial.
(50/87)
In 25 neurological patients with detrusor hyperreflexia terodiline reduced the number of total micturitions during daytime. Bladder capacity was increased and amplitude of the bladder contractions was reduced. An increase in residual urine was also observed. Mild anticholinergic side-effects were measured on pupillary motility and on heart rate variation. It is concluded that terodiline is a useful alternative in treatment of patients with detrusor hyperreflexia. (+info)
Some observations on the -adrenoceptor agonist properties of the isomers of salbutamol.
(51/87)
1. The pharmacological activities of the optical isomers of salbutamol have been examined. (-)-Salbutamol was much more potent than (+)-salbutamol on beta-adrenoceptors.2. Both (-)- and (+)-salbutamol showed high selectivity for beta-adrenoceptors in bronchial muscle compared to cardiac muscle, in this way resembling racemic salbutamol.3. The use of isomeric activity ratio to detect differences between receptors was examined in the light of the results obtained with the isomers of salbutamol. (+info)
Clinical investigation of an antagonist at alpha- and beta-adrenoceptors-AH5158A.
(52/87)
1. The alpha- and beta-adrenoceptor blocking action of AH 5158A was investigated in man using the veins of the hand, the arterial bed of the forearm, and certain responses of the circulation as a whole.2. In the veins, locally infused AH 5158A resulted in specific and competitive antagonism of the constrictor response to locally infused noradrenaline and of the dilator response to isoprenaline.3. Brachial artery infusions of AH 5158A resulted in competitive antagonism of the arterial blood flow changes produced by local infusions of noradrenaline and isoprenaline.4. Systemic infusion of AH 5158A (0.5-0.9 mg/kg) produced clear blockade of the heart rate response to systemic infusion of isoprenaline. It also attenuated the response to exercise at 80 watts for 4 min; mean arterial pressure during exercise was reduced by 16% and heart rate by 18%. Blockade lasted at least 1 hour.5. AH 5158A caused small changes in arterial pressure and heart rate at rest supine, but had no effect on the response of pressure and rate to tilting. (+info)
The effects of a new alpha- and beta-adrenoceptor antagonist (AH5158) upon the general and coronary haemodynamics of intact dogs.
(53/87)
AH5158, a salicylamide derivative, said to be a blocker of alpha- and beta-adrenoceptors, has been studied in intact anaesthetized dogs. At a dose of 2.5 mg/kg intravenously, the drug increased cardiac output and caused a late fall in mean systemic and pulmonary arterial pressure. Coronary sinus flow increased, as did cardiac oxygen extraction. External cardiac efficiency decreased. Blood glucose and non-esterified fatty acid values increased, but cardiac extraction of these did not change. (+info)
Inhibition by diuretics of cyclic 3',5'-AMP-dependent protein kinase from toad bladder epithelium.
(54/87)
1. A cAMP-dependent protein kinase enzyme has been isolated from toad bladder epithelium.2. This enzyme catalyses the phosphorylation of histones; a reaction stimulated by 0.1 muM cAMP.3. Activity of this enzyme in the presence of 0.1 muM cAMP was significantly inhibited by 100 muM mercuderamide, bumetanide and frusemide. A small, though statistically insignificant inhibition was seen with the same concentrations of hydrochlorothiazide and ethacrynic acid.4. The half maximal inhibition was achieved with mercuderamide, 5 muM, and with frusemide and bumetanide 600 muM. (+info)
Kinetic studies of glutamate dehydrogenase with glutamate and norvaline as substrates. Coenzyme activation and negative homotropic interactions in allosteric enzymes.
(55/87)
1. Kinetic studies of glutamate dehydrogenase were made with wide concentration ranges of the coenzymes NAD(+) and NADP(+) and the substrates glutamate and norvaline. Initial-rate parameters were evaluated. 2. Deviations from Michaelis-Menten behaviour towards higher activity were observed with increasing concentrations of either coenzyme with glutamate as substrate, but not with norvaline as substrate. 3. In phosphate buffer, pH7.0, Lineweaver-Burk plots with either coenzyme as variable and a constant, large glutamate concentration showed three or four linear regions of different slope with relatively sharp discontinuities. Maximum rates obtained by extrapolation and Michaelis constants for the coenzymes increased in steps with increase of coenzyme concentration. 4. In the absence of evidence of heterogeneity of the enzyme and coenzyme preparations, the results are interpreted in terms of negative homotropic interactions between the enzyme subunits. It is suggested that sharp discontinuities in Lineweaver-Burk plots or reciprocal binding plots may be characteristic of this new type of interaction, which can be explained in terms of an Adair-Koshland model, but not by the model of Monod, Wyman & Changeux. (+info)
Trial of new bronchodilator, terbutaline, in asthma.
(56/87)
Terbutaline, a new bronchodilator acting on beta-adrenergic receptors, was given to 10 asthmatic patients, who received on separate days 5 mg orally, 10 mg orally, and 0.25 mg subcutaneously. The ventilatory response was assessed by measurement of the FEV(1) before and at intervals after administration. The cardiovascular response was assessed by measurement of the heart rate and blood pressure and by electrocardiography at the same times as spirometry was performed.The ventilatory response to all three doses and by both routes was satisfactory. The maximal increase in FEV(1) after 5 mg orally was only slightly less than that after 10 mg. The maximal increase in heart rate after 5 mg orally was about half that which occurred after 10 mg. It is concluded that 5 mg orally and 0.25 mg subcutaneously are suitable doses.In general a modest fall in blood pressure affected the diastolic more than the systolic. On E.C.G. the T wave was often depressed, and in one patient, it was inverted. A trough-like depression of the QRS baseline occurred several times. The significance of the E.C.G. changes is uncertain. (+info)