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)

(-)-3/-Norepinephrine (3H-NE) binding to the microsomal fraction of the rabbit aorta has been studied. Binding appears to increase linearly with time up to at least 30 min, shows no evidence of stereoselectivity and may be inhibited only by compounds possessing the catechol or 3-methoxy-4hydroxyphenyl moieties, with the latter being 100-fold less effective. 3H-NE binding is saturable with a Km of 8.5 X 10(-8) M and V max of 28 pmoles/mg protein. A Hill plot indicates that binding is noncooperative whereas a Scatchard plot suggests that two sites may be present. Binding does not appear to require physiological concentrations of Ca2+ or Mg2+ and is inhibited significantly by EDTA and sodium metabisulfite. In addition, binding is markedly enhanced by low and high pH values. This binding is also inhibited by sodium metabisulfite which suggests that an oxidized form of the catecholamine is the active binding species. Experiments with several group specific reagents indicate that binding may require a free sulfhydryl group but not a carboxyl function. The binding process requires an energy of activation of 14.8 kcal/mole whose magnitude may be partly explained, with the aid of optical rotatory dispersion spectra, by a non-stereoslective conformational change in protein structure induced by the amine. The characteristics of the 3H-NE binding sites observed in the microsomal fractional of the rabbit aorta appear to be different from those expected if binding were to the adrenoreceptors. A possible mechanism for catecholamine binding to free sulfhydryl groups on protein is presented.
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PMID:A kinetic analysis of a catechol-specific binding site in the microsomal fraction from the rabbit aorta. 0 20

1. The membrane potential of the smooth muscle cells of the rabbit main pulmonary artery amounts to -57 mV, the length constant of the tissue is 1.48 mm and the time constant of the membrane 182 msec. On the basis of the electrical properties of its membrane, this smooth muscle tissue is classified as a single-unit type. During outward current pulses, the membrane shows marked rectification and action potentials can never be generated.2. Tetraethylammonium (10 mM) and procaine (5 mM) depolarize the membrane and increase the membrane resistance. By studying the effect of both substances on the (42)K efflux, it could be concluded that they reduce the K-permeability of the membrane. They also suppress the rectification of the membrane and increase the length constant of the membrane. In the presence of TEA and procaine, a graded response of the membrane can be induced by outward current pulses, but overshoot potentials never occur.3. Noradrenaline, in concentrations between 2 x 10(-8) and 10(-7)M, evokes contraction without depolarizing the membrane. When the concentration is increased above 2 x 10(-7)M, noradrenaline depolarizes the membrane and reduces the membrane resistance. A study of the effect of noradrenaline on the K, Cl and Na fluxes has revealed that it increases the permeability of the membrane for these three ions.4. The tissue concentrations of Na and K are 80 and 38 m-mole/kg wet wt., respectively. The amount of Cl in the cellular compartment was measured by an extrapolation procedure and found to be 13 m-mole/kg wet wt. The extracellular space measured with [(14)C]sorbitol is 550 ml./kg wet wt. and the dry wt./wet wt. ratio 19%. The calculated equilibrium potentials for K, Na and Cl (E(K), E(Na) and E(Cl)) are -83, +59 and -26 mV, respectively. In efflux experiments under steady-state conditions, the following rate constants have been calculated: 0.092 min(-1) for Na, 0.029 min(-1) for Cl and 0.0054 min(-1) for K. The calculated value for the ratio P(Na)/P(K) was 0.22 and for P(Cl)/P(K) 0.63.5. K-free solution and 2 x 10(-6)M ouabain depolarize the cells by about 8 mV. After exposure of the cells to K-free solution, they hyperpolarize on readmission of K, suggesting that part of the membrane potential could be due to electrogenic transport of ions.6. A decrease of external Ca depolarizes the cells and increases the membrane resistance. Na-deficiency hyperpolarizes these smooth muscle cells but this procedure does not prevent the depolarization induced by Ca deficiency.
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PMID:The membrane properties of the smooth muscle cells of the rabbit main pulmonary artery. 91 33

1. Noradrenaline release and radioligand binding studies were carried out in the cat hypogastric nerve ligated in vito 2 cm distal to the inferior mesenteric ganglion for different time periods, and in different effector organs.2. Large quantities of noradrenaline and dopamine beta-hydroxylase (DBH) accumulated in the segments of nerve immediately proximal (P(1)) and distal (D(1)) to the ligation, with rates of about 100 and 25 mm/24 hr for the orthograde and retrograde transport, respectively.3. Nicotine evoked the release of noradrenaline from P(1) and atrial slices; the secretory response to nicotine was completely antagonized by mecamylamine. [(3)H]alpha-bungarotoxin biding to membranes from P(1) allowed the estimation of a K(D) of 2.97 nm and a B(max) of 1639 f-mole/mg protein.4. Acetylcholine inhibited the release of endogenous noradrenaline evoked by high K(+) stimulation in atrial slices, but not in P(1) segments. Similarly, carbachol decreased [(3)H]noradrenaline release induced by electrical stimulation (twenty-six shocks, 2 Hz, 5 msec) in the atrium but not in P(1).5. [(3)H]Quinuclydinilbenzylate ([(3)H]QNB) specifically binds to membranes from P(1) and vas deferens, following a saturation curve. In the case of P(1) segments taken 48 hr after ligation a K(D) of 0.35 nm and a B(max) of 129 f-mole/mg protein were found.6. The fact that the B(max) in P(1) and D(1) increased with the time of ligation suggests that orthograde and retrograde axonal transports of muscarinic binding sites exist in this nerve, with approximate rates of transport of 15 and 8 mm/24 hr, respectively.7. As far as adrenoceptors are concerned, we observed that yohimbine or phentholamine did not modify transmitter release from P(1), evoked by high K(+) or electrical stimulation. However, yohimbine enhanced the release of [(3)H]noradrenaline induced by electrical stimulation from splenic slices of the same animals.8. [(3)H]Clonidine, [(3)H]dihydroergocryptine or [(3)H]dihydroalprenolol ([(3)H]DHA) did not specifically bind to membranes from P(1), in spite of the fact that they showed typical saturation curves for specific binding in cortex and atrial membranes from the same cats.9. In conclusion, these data (a) further show that the ligated hypogastric nerve is a good model of noradrenergic nerve terminal free of effector cell; (b) provide direct evidence for the neural location of nicotinic receptors whose activation trigger noradrenaline release from noradrenergic neurones; (c) demonstrate the neural location and axonal transport of muscarinic receptor sites, but leave certain doubts about its functional role in this noradrenergic neurone; and (d) do not support the hypothesis that alpha and beta-adrenoceptors which modulate noradrenaline release from peripheral noradrenergic nerve terminals are neurally (or prejunctionally) located.
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PMID:Presence and axonal transport of cholinoceptor, but not adrenoceptor sites on a cat noradrenergic neurone. 618 90

In order to investigate the actions of acetylcholine (ACh), catecholamines and substance P on K transport in the submaxillary gland, measurements of net K flux to and from the gland tissue using flame photometry, Na efflux from the tissue using radioactive 22Na, and membrane potential and input resistance using micro-electrodes were carried out on isolated superfused segments of rat and mouse submaxillary glands. ACh (5.5 X 10(-8) to 5.5 X 10(-4) M), phenylephrine (5 X 10(-7) to 5 X 10(-4) M) or substance P (10(-9) to 10(-5) M) stimulation for 5 min induced a transient K release followed by a small K uptake after the cessation of stimulation. The K release was markedly enhanced by the simultaneous addition of ouabain (10(-3) M). On the other hand, isoprenaline (2.5 X 10(-9) to 2.5 X 10(-5) M) induced a transient K uptake without any preceding K release. The K uptake was completely blocked by the addition of ouabain. Noradrenaline induced only K uptake at a low concentration (3 X 10(-7) M), but induced transient K release followed by marked K uptake at higher concentrations (3 X 10(-6) to 3 X 10(-4) M). The K release induced by noradrenaline was suppressed by the addition of phentolamine (10(-5) M), while the K uptake was suppressed by propranolol (5 X 10(-6) M). The K release induced by ACh, phenylephrine, noradrenaline or substance P was severely reduced by Ca omission from the superfusing solution and restored by the re-admission of Ca. The isoprenaline- or noradrenaline-induced K uptake was, however, little affected by Ca omission. Application of isoprenaline (2.5 X 10(-6) M) induced an increase in 22 Na efflux. The increase in 22Na efflux was completely abolished in the presence of ouabain. Local application to the tissue bath of isoprenaline (4.7 X 10(-13) to 4.7 X 10(-12) mole) or noradrenaline (5.7 X 10(-12) to 5.7 X 10(-11) mole) in the presence of phentolamine (10(-5) M) induced membrane hyperpolarization without any appreciable change in input resistance. The hyperpolarization was abolished in the presence of ouabain (10(-3) M) or propranolol (5 X 10(-6) M) or in a K-free or low Na solution. Higher doses of both agonists, however, induced depolarization or biphasic responses (initial depolarization followed by hyperpolarization). The depolarizations were accompanied by a moderate reduction in input resistance. It is concluded that in the rat and mouse submaxillary gland acinar cells cholinergic, alpha-adrenergic or substance P stimulation causes K release (and perhaps Na uptake) resulting in activation of the Na-K pump, while beta-adrenergic receptor stimulation might directly activate the Na-K pump resulting in K uptake, or might cause Na uptake resulting in activation of the Na-K pump.
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PMID:Activation of potassium transport induced by secretagogues in superfused submaxillary gland segments of rat and mouse. 619 88

The interaction of agonists and antagonists with alpha 1-adrenergic receptors in rat vas deferens was examined using radioligand binding assays and contractility measurements. 125I-Labeled BE 2254 (125IBE) was found to bind rapidly and reversibly to a single class of high-affinity binding sites in homogenates of rat vas deferens. The k1 for association was 3.8 X 10(7) 1/mole-sec, the k-1 for dissociation was 2.3 X 10(-3) sec-1, and the KD was 105 pM. The order of potency for antagonists inhibiting 125IBE binding was prazosin greater than indoramin greater than phentolamine greater than yohimbine. Norepinephrine, phenylephrine, and other alpha-adrenergic agonists produced dose-dependent contractions of whole vas deferens in vitro. This contractile response was competitively inhibited by alpha-adrenergic blocking drugs with the same potency order observed for inhibition of specific 125IBE binding. Comparison of pA2 values for alpha 1- and alpha 2-selective antagonists competitively inhibiting contractile responses to norepinephrine, epinephrine, or phenylephrine suggested that these drugs caused their contractile effects solely through alpha 1-adrenergic receptors, and that there were no alpha 2-adrenergic receptors mediating contraction in this tissue. The pA2 values for antagonist inhibition of alpha-adrenergic receptor-mediated contractile responses were highly correlated (r = 0.995) with the KD values for antagonist inhibition of 125IBE binding in this tissue. The EC50 values for partial agonists were also highly correlated with the KD values for inhibition of 125IBE binding in vas deferens. However, the EC50 values of full agonists in causing contraction were in general 10- to 100-fold lower than the KD values for inhibiting 125IBE binding, possibly representing a substantial "spare receptor" population in this tissue. The results suggest that rat vas deferens contains a homogeneous population of alpha 1-adrenergic receptors mediating the contractile response to norepinephrine, that these receptors can be directly labeled with 125IBE, and that there may be a nonlinear relationship between agonist occupancy of alpha 1-adrenergic receptors and the functional response of this tissue.
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PMID:Occupancy of alpha 1-adrenergic receptors and contraction of rat vas deferens. 630 Jun 45

1. Plasma and adipose tissue purine nucleosides were assayed by reversed phase high-performance liquid chromatography after purification of the samples on phenylboronate affinity gel. 2. The adenosine content of unstimulated subcutaneous adipose tissue was close to 1 n-mole/g. The concentrations of adenosine and inosine in canine arterial plasma were 0.26 +/- 0.03 and 0.16 +/- 0.03 microM, respectively. In venous plasma from the canine subcutaneous adipose tissue the corresponding values were 0.32 +/- 0.04 and 0.28 +/- 0.06 microM under basal conditions. The arterio-venous concentration difference of adenosine was linearly dependent upon the arterial adenosine concentration. At arterial concentrations below 0.3 microM there was a net production of adenosine; above 0.3 microM there was a net extraction of approximately 77% of the adenosine. Adenosine was extensively eliminated in blood. The major part of this elimination could be accounted for by metabolism to inosine, hypoxanthine and uric acid. 3. Following sympathetic nerve stimulation (4 Hz for 20 min) the rate of adenosine outflow from adipose tissue increased from 0.33 +/- 0.22 to a peak value of 1.2 +/- 0.26 n-mole/min. This corresponds to a net release of 8.7 +/- 3.0 n-mole/100 g tissue. Inosine outflow rose from 0.64 +/- 0.37 to 5.3 +/- 1.4 n-mole/min, corresponding to a net release of 24.6 4/- 8.7 n-mole/100 g. Nerve stimulation also increased the release of [3H]purines from [3H]adenine pre-labelled adipose tissue. The fractional release increased 15-fold after stimulation. The radioactivity was mainly in the form of hypoxanthine, inosine and uric acid while adenosine was a minor component. When metabolism in blood was inhibited by dipyridamole and an adenosine deaminase inhibitor nerve-stimulation-induced release of [3H]purines was mainly in the form of adenosine. 4. Noradrenaline injection also induced a release of radioactive purines and of inosine. On the other hand, the outflow of endogenous adenosine was very small. 5. The present results demonstrate that under basal conditions adenosine is present in arterial and venous canine plasma. The free extracellular tissue level may be similar to the basal arterial adenosine concentration. Sympathetic nerve stimulation and noradrenaline induces a marked release of adenosine which is rapidly metabolized in the tissue and blood stream to inosine, hypoxanthine and uric acid. In adipose tissue the levels of adenosine reached after adrenergic stimulation appear high enough to be of physiological relevance.
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PMID:The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline. 727 25