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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have examined the effects of four dendrotoxin (DaTX) peptides, alpha-, beta-, gamma- and delta-DaTX, separated from the venom of the green mamba (Dendroaspis angusticeps), on field stimulation-evoked [3H]noradrenaline (NA) release from rat hippocampus and compared their effects with those of two other inhibitors of K+ channels, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). 4-AP (10-300 microM) and TEA (0.1-5 mM) facilitated the evoked [3H]NA release in a concentration-dependent manner. The evoked [3H]NA release was reduced to about half by alpha 2-adrenoceptor stimulation (UK 14,304; 100 nM) and this reduction was antagonized by 4-AP (10-100 microM), whereas TEA even at 5 mM was a poor inhibitor of alpha 2-effects. alpha-DaTX (10-200 nM) mimicked 4-AP in increasing the electrically evoked [3H]NA release and diminishing the inhibitory effects of UK 14,304 in a concentration-dependent manner. delta-DaTX did not itself alter the electrically evoked [3H]NA release, but at 200 nM, it reduced the effects of alpha 2-receptor stimulation. beta- and gamma-DaTX (up to 200 nM) had no significant effects. 4-AP, 3,4-diaminopyridine (3,4-DAP), TEA and the four dendrotoxins displaced the binding of [3H]p-aminoclonidine ([3H]PAC) from alpha 2-receptors. The IC50 values were 6.6 x 10(-4), 1.42 x 10(-3), 5.6 x 10(-2) for 4-AP, 3,4-DAP and TEA, respectively, and 3.19 x 10(-6) M for alpha-DaTX. Thus, their potency as inhibitors of alpha 2-receptors is apparently too low to account alone for the antagonism by K+ channel inhibitors of alpha 2-effects on NA release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the effects of four dendrotoxin peptides, 4-aminopyridine and tetraethylammonium on the electrically evoked [3H]noradrenaline release from rat hippocampus. 168 82

Norepinephrine (NE), acting through alpha 2-noradrenergic receptors in the hypothalamic paraventricular nucleus (PVN), has been implicated in the control of feeding behavior and body weight gain. To determine whether this hypothalamic receptor system is disturbed in genetically obese rats, the binding of radioligands to alpha 2-noradrenergic, as well as to alpha 1-noradrenergic, receptors was examined in seven hypothalamic nuclei of obese Zucker rats relative to their lean littermates. Receptor binding procedures, using the alpha 2-noradrenergic agonist [3H]p-aminoclonidine ([3H]PAC) and the alpha 1-noradrenergic antagonist [3H]prazosin, demonstrated that the obese rats, compared to the lean rats, had significantly greater alpha 2-noradrenergic and alpha 1-noradrenergic receptor binding, specifically in the PVN as opposed to other hypothalamic areas examined. Moreover, the obese rats, compared to the lean rats, exhibited greater responsiveness to the effects of food deprivation (48 h), which caused a significant decline in radioligand binding to both alpha 2 and alpha 1 receptors, specifically in the PVN. A decrease in alpha 2-receptor binding after deprivation in the obese rats was also seen in two basal hypothalamic areas, namely, the supraoptic nucleus and arcuate nucleus-median eminence. The possibility exists that these disturbances in hypothalamic alpha-receptors may be involved in the development and/or maintenance of the genetic obesity.
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PMID:Higher alpha-noradrenergic receptors in paraventricular nucleus of obese Zucker rats: decline after food deprivation. 168 67

Clonidine, an agonist of central alpha-2-adrenergic receptors, reduced the peripheral sympathetic activity. With regard to the mutual pathophysiological relationship of blood pressure regulating mechanisms, the authors wanted to find out whether after clonidine administration, in addition to the known suppression of catecholamine levels (CA), also changes in the concentration of other pressor and depressor humoral substances will occur. They investigated therefore in 15 patients with essential hypertension (EH) and in three patients with pheochromocytoma the urinary excretion of free noradrenaline (NA), adrenaline (A) and dopamine (DA), the plasma renin activity (PRA), the aldosterone concentration (PAC) and atrial natriuretic factor (ANF) in plasma, using radioimmunoanalysis, always before and 24 hours after clonidine administration (Haemiton retardR) by the oral route. Its administration led in patients with EH to a decline of NA and DA. On the other hand, in pheochromocytoma their urinary excretion did not change in an unequivocal way, and when it declined, never normal NA and DA levels were reached. A excretion remained unaltered in both groups of patients. The drop of PRA after clonidine as a result of the drop of peripheral adrenergic activity was not associated with an expected parallel drop of PAC but by its rise. This effect can be explained by a reduction of the tonic inhibition of PAC output when the DA level declines. The rise of ANF after clonidine administration will be the subject of subsequent investigations. It cannot be ruled out that this effect is due to the direct action of clonidine on alpha receptors in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of clonidine on humoral factors in patients with arterial hypertension]. 214 Feb 96

Binding sites labeled by [3H]p-aminoclonidine ([3H]PAC) were characterized in bovine brain membranes prepared from the ventrolateral medulla, the probable site of the antihypertensive action of clonidine and analogs. Comparison was made with [3H]PAC binding to membranes prepared from frontal cortex, which has been studied extensively. Saturation binding isotherms for [3H]PAC were similar in the two regions, although Bmax values were approximately two-fold lower in ventrolateral medulla relative to frontal cortex. Norepinephrine and other phenylethylamines displaced [3H]PAC from a maximum of 70% of the total sites in the ventrolateral medulla. The remaining 30% were norepinephrine-insensitive, non-adrenoceptor sites which displayed high affinity for imidazole compounds. Ligand selectivity differed markedly between ventrolateral medulla and frontal cortex, since some imidazole compounds which potently inhibited [3H]PAC binding in the ventrolateral medulla had no effect in frontal cortex. Imidazole binding sites may mediate, in part, the hypotensive action of clonidine and other imidazole compounds in the ventrolateral medulla. These sites may also participate in the functions of a putative endogenous clonidine-like substance.
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PMID:Clonidine binds to imidazole binding sites as well as alpha 2-adrenoceptors in the ventrolateral medulla. 303 Jul 79

CA levels, PRA, PAC responses to low and high sodium dialysates in haemodialysed patients were investigated. Increased levels of dopamine (DA), adrenaline (A) and noradrenaline (NA) were found during dialysis and ultrafiltration with high sodium dialysate (148 mEq/l), and significantly higher PRA with low sodium dialysate (131 mEq/l). PAC slightly but significantly decreased during dialysis with low sodium dialysate and significantly increased during ultrafiltration. The present results suggest that sodium dialysate concentration has a significant influence on the function of the autonomic system, PRA and PAC in haemodialysed patients.
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PMID:High and low sodium acetate haemodialysis and ultrafiltration. II. Comparison of plasma renin activity (PRA), catecholamine levels (CA) and plasma aldosterone concentration (PAC). 353 26

Sixteen patients (11 M, 5 F), median age 41 years, with essential hypertension insufficiently controlled on hydrochlorothiazide 75 mg/day (DBP greater than or equal to 100 mmHg) were investigated. Plasma renin concentration (PRC), angiotensin II concentration (PA II), aldosterone concentration (PAC), plasma noradrenaline concentration (PNAC), plasma volume (PV) and exchangeable sodium (NaE) were determined and a saralasin-infusion (5.4 nmol/kg/min) was carried out while the patients were on thiazide alone, and in fourteen cases, repeated 3 months later after addition of a beta-blocker (propranolol 6, metoprolol 6 and atenolol 2 patients). On thiazide alone PRC, PA II and PAC was higher than normal in the group as a whole and the angiotensin II-inhibitor, saralasin, caused a significant decrease in MAP in twelve out of sixteen patients. After addition of a beta-blocker SBP and DBP decreased from 164/109 mmHg to 136/94 mmHg. PRC and PA II decreased by 40% and 58%, respectively. At this point saralasin caused no significant change in MAP. No close correlation was found between changes in BP on beta-blocker treatment and either PRC, PA II or saralasin response on thiazide treatment. PV, NaE, PAC and PNAC did not change sigificantly. It is concluded that in pts with thiazide-induced stimulation of the renin-angiotensin system (RAS) addition of a beta-blocker leads to suppression of RAS and the angiotensin II dependence of the blood pressure is nearly abolished. This mechanism might well contribute to the antihypertensive effect of beta-blockade in this particular situation. However, the pharmacological changes induced by beta-blockade are very complex, and most likely other factors are involved in the antihypertensive effect of beta-blocking drugs.
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PMID:Angiotensin II blockade during combined thiazide-beta-blocker treatment. 610 82

The labelling of rat cerebral cortex alpha 2-adrenoceptors with [3H]-yohimbine ([3H]-YOH) was investigated. At 25 degrees C, binding equilibrium was reached in about 10 min and dissociation occurred with a half time of about 1 min. Saturation experiments gave an equilibrium KD value of 10.13 +/- 1.95 nM and a maximum number of sites of 254 +/- 22 fmol/mg protein. The [3H]-YOH binding sites exhibited alpha 2-adrenergic receptor specificity; the order of potency for the antagonists was rauwolscine greater than yohimbine much greater than prazosin greater than corynanthine. For the agonists, the order was: oxymetazoline greater than clonidine greater than (-)-adrenaline greater than (-)-noradrenaline much greater than (-)-phenylephrine. Agonists exhibited shallow curves in inhibiting [3H]-YOH binding, with pseudo-Hill coefficients (nH) of less than 1.0. These curves were shifted to lower overall affinity and steepened in the presence of 100 microM GTP. Antagonist competition curves were also shallow but GTP had no significant effect. Divalent cations at millimolar concentrations decreased the [3H]-YOH binding: IC50 values were about 6.0, 6.8 and 0.3 mM for Ca2+, Mg2+ and Mn2+ respectively. The maximal number of [3H]-YOH binding sites in the cortex was close to that labelled by the agonist [3H]-paraaminoclonidine ([3H]-PAC). The regional distribution of these sites in the brain, examined at a single concentration of [3H]-YOH and [3H]-PAC, showed a similar pattern except in the striatum. Taken together, the results indicate that like [3H]-PAC, [3H]-YOH labels alpha 2-adrenoceptors in rat brain cortex. They also show that [3H]-YOH is a useful tool for the study of the high and low affinity sites.
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PMID:Characteristics of the [3H]-yohimbine binding on rat brain alpha2-adrenoceptors. 630 Jul

To evaluate the role of the central nervous system on the furosemide-induced increases in plasma noradrenaline (PNA), renin activity (PRA), and aldosterone concentration (PAC), central vasoactive sympathetic structures were inhibited by intravertebral artery infusion of colnidine. Intravertebral artery infusion of clonidine (0.06 microgram/Kg/min) significantly reduced basal PNA, heart rate, and arterial pressure, while both PRA and PAC were increased. Intravenous infusion of the same dose of clonidine caused no significant changes in PNA, PRA, and PAC. Intravertebral artery infusion of clonidine (0.02 or 0.1 microgram/Kg/min) significantly suppressed the furosemide-induced increases in PNA and heart rate, and induced a drop in arterial pressure. Although the furosemide-induced increase in PRA was suppressed by intravertebral artery infusion of clonidine, the furosemide-induced increase in PAC was not affected. These results suggest that the furosemide-induced increase in PNA may be mediated by the central sympathetic nervous system and that some of the furosemide-induced increase in PRA may be mediated by central sympathetic neural activation.
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PMID:Contributions of central sympathetic neural activity to furosemide-induced increases in plasma renin activity and noradrenaline. 634 67

Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.
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PMID:Prostaglandins, renin, aldosterone, and catecholamines in preeclampsia. 636 75

Urinary excretion of prostaglandin E2 (PGE2) and F2 alpha (PGF2 alpha), plasma concentrations of renin (PRC), aldosterone (PAC), noradrenaline (PNA) and adrenaline (PA) were determined in the third trimester of pregnancy, 5 days and 3 months after delivery in preeclampsia and normotensive pregnant and non-pregnant control subjects. PGE2 was higher in pregnant control subjects than in non-pregnant subjects, but reduced to non-pregnant level in preeclampsia. PGF2 alpha was the same in preeclampsia and normotensive pregnancy but higher than in the non-pregnant group. PRC and PAC were increased during pregnancy, but considerably lesser in preeclampsia than during normotensive pregnancy. PNA and PA were the same in all three groups. All parameters were normal 3 months after delivery. There were no correlations between any of the hormones and blood pressure in any of the groups. PGE2 was positively correlated to PRC. The lack of renal PGE2 in preeclampsia might be responsible for the decrease in renal blood flow and sodium excretion, and the changes in PRC and PAC are supposed to be secondary to changes in PGE2. It is hypothesised that preeclampsia is a state of prostaglandin deficiency.
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PMID:Prostaglandins, catecholamines, renin and aldosterone during hypertensive and normotensive pregnancy. 675 44


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