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)

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

The stoichiometry of the copper requirement for the dopamine beta-monooxygenase-catalyzed conversion of dopamine to norepinephrine has been investigated by rapid chemical-quench techniques. This approach, which employs concentrated samples of enzyme, overcomes ambiguities of interpretation arising from levels of trace copper in excess of enzyme concentrations normally added to steady state kinetic assays. Low turnover numbers are observed when rapid quench kinetic studies are performed under conditions in which enzyme concentrations (2.5-7.1 microM) are in excess over trace copper levels (about 0.7 microM). The addition of exogenous Cu(II) results in full restoration of activity, which is maximal at a stoichiometry of 2 mol of copper/mol of enzyme subunit. From the dependence of catalytic activity on copper levels we conclude that both coppers are required for catalysis. No stimulation of activity was observed upon addition of the following metal ions: Ni(II), Co(II), Mn(II), Fe(III), and Zn(II). In addition, the magnitude of the tritium isotope effect for [2-3H]dopamine hydroxylation is invariant over a large range of enzyme activities accompanying changes in the ratio of copper to enzyme concentration. These results appear to rule out an effector role for the second mole of copper/subunit, implicating both copper atoms in active site redox chemistry.
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PMID:Evidence for two copper atoms/subunit in dopamine beta-monooxygenase catalysis. 670 64

Bovine adrenomedullary granules were separated into two subfractions by isopycnic density centrifugation. A small subfraction (approximately 10% of the total population) was sedimented into 2.2 M sucrose while the main population (80% of the total) was recovered at the interphase between 1.6 and 2.2 M sucrose. The concentrations of catecholamine (CA) and calcium showed marked seasonal variations for both subfractions, with lowest levels in the spring and highest levels in the winter. Throughout the year the concentrations of CA and calcium were 2-3 times higher in the minor subpopulation which also accounted for an abundance of noradrenaline (NA); on average 68% NA of total CA, 6.6 mumol CA and 225 nmol calcium/mg protein. The two subpopulations stored CA in similar ratios to ATP and calcium; i.e. 30 mol CA: 4 mol ATP: 1 mol Ca2+, indicating storage of CA largely independent of an equivalent amount of ATP, at least during winter when CA storage was 3.3 and 9.9 mumol/mg protein in the major and minor subpopulation respectively. The two subpopulations differed significantly in ratio of releasable dopamine beta-hydroxylase (DBH) activity per mole CA due to insignificant differences in specific activity of releasable DBH (0.4 unit/mg protein). The results show: (1) that the adrenomedullary granules are heterogeneous with respect to releasable activity of DBH per mole CA and subject to considerable seasonal variations; (2) a large portion of the NA-storing granules has a high concentration of releasable constituents; (3) both adrenaline (A)- and NA-storage are closely associated with that of calcium and occur in excess of that balanced by equivalent amounts of ATP.
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PMID:Heterogeneity in the adrenomedullary storage of catecholamines, ATP, calcium and releasable dopamine beta-hydroxylase activity. 725 54