Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Labetalol was given to women with hypertension of pregnancy in their last trimester to study its acute effect on circulation and metabolism. Seven women were given 50 mg labetalol i v. There was a significant decrease of blood pressure from a mean of 143/101 +/- 4/2 (SEM) to 127/88 +/- 5/2 mm Hg. Maternal heart rate fell significantly from 77 +/- 5 to 68 +/- 3 beats per min. These changes persisted during a three-hour observation period. The hypotensive response was accompanied by a significant increase in plasma noradrenaline from 1.54 +/- 0.16 to 2.37 +/- 0.41 nmol/l, suggesting sympathetic activation. Plasma cyclic AMP, which is increased by beta 2-adrenoceptor stimulation, was significantly elevated after labetalol. This supports the hypothesis of partial beta-agonist activity of labetalol. Lipid metabolism, as judged from measurements of plasma FFA, glycerol and 3-hydroxybuturic acid, showed little change. The acute effect of labetalol on uteroplacental blood flow was determined in eight women with pregnancy hypertension using a gammacamera on line with a computer. 0.5 mCi indium-113m was given i v before and 30 min after labetalol was administered i v in a dose of 1 mg per kg body weight. After the injections of indium-113m, serial scintigrams were recorded during 10 s periods for 240 s. By computerized summation of the scintigrams, an image was obtained in which the placenta could be outlined for time-activity analysis of the isotope accumulation curve. From this curve a uteroplacental blood flow index could be calculated. Labetalol induced a significant drop of mean arterial blood pressure from 114 +/- mm Hg to 100 +/- 3 mm Hg after 30 min in this group of women. However, the uteroplacental blood flow index did not change. As we have earlier shown with this technique that uteroplacental blood flow can be severely impaired in hypertension of pregnancy, the finding of substained uteroplacental blood flow simultaneously with a decrease in blood pressure should be of clinical importance. Taken together with other studies of clinical effects, these results indicate that labetalol is useful in the treatment of hypertension of pregnancy.
 ...
PMID:Labetalol, a combined alpha- and beta-blocker, in hypertension of pregnancy. 696 61

In contrast to cyclic AMP-dependent positive inotropes, the calcium-sensitizer and partial phosphodiesterase (PDE) inhibitor pimobendan may induce beneficial effects in heart failure. However, its effect on relaxation, myocardial energetics and neurohormones are unknown. Twelve patients with heart failure, New York Heart Association (NYHA) classification II-III, due to ischemic cardiomyopathy, were studied for 1 h after they received 5 mg pimobendan intravenously (i.v.). Pimobendan progressively reduced systemic resistance and left ventricular end-diastolic pressure (LVEDP) (22 and 50%, respectively) and improved isovolumetric contractility and relaxation parameters by 30% (all p < 0.05 vs. control). LV end-diastolic and end-systolic volumes (LVEDV, LVESV) decreased significantly by 20 and 19%, respectively. Cardiac output (CO) increased by 17% due to a simultaneous increase in heart rate (HR) from 75 +/- 3 to 86 +/- 5 beats/min (mean +/- SEM, p < 0.05). Pimobendan did not change coronary hemodynamics, but myocardial O2 extraction and consumption were decreased significantly by 18 and 20%, respectively. Catecholamines, angiotensin II (AII), and aldosterone levels did not change significantly. In contrast, arterial and coronary venous renin increased significantly from 57 +/- 17 and 53 +/- 14.7 microM/h at control to 69 +/- 20 and 69 +/- 20 microM/h, respectively, 60 min after pimobendan administration. Simultaneously, cardiac renin uptake at baseline (0.449 +/- 0.185 mumol/min) changed to release (-0.071 +/- 0.145 mumol/min, p < 0.05). Serious side effects did not occur. Thus, pimobendan had progressive positive inotropic and lusitropic effects, diminished preload and afterload despite modest stimulation of plasma renin activity (PRA), and reduced systemic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hemodynamic, neurohumoral, and myocardial energetic effects of pimobendan, a novel calcium-sensitizing compound, in patients with mild to moderate heart failure. 753 50

One of the most important research topics in plastic surgery is the extension of the length of skin flaps that survive. We have investigated the increase in the length of skin flaps that can be achieved by giving dibutyryl cyclic AMP (DB-cAMP) to rabbits with experimental skin flaps and compared the results with those in animals not given DB-cAMP. Three variables, the arrival of DB-cAMP in the critical area of circulation of the flap (n = 6), changes in the blood flow in the flap (n = 10), and increase in the length of skin flap that survived (n = 30) were investigated by high performance liquid chromatography and laser Doppler flowmetry. DB-cAMP reached the critical area of circulation in the skin flap (dye distance), increased the blood flow within this area (mean (SEM) peak value 30 minutes after operation 1.24 (0.06) ml/min/kg compared with 1.06 (0.02) in control flaps), and extended the length of the flap that survived (mean (SEM) length seven days after operation 66.1 (3.0) mm compared with 60.8 (1.8) mm in the control group). We conclude that DB-cAMP improved the blood flow in skin flaps in rabbits with a consequent increase in the length of skin flap that survived.
 ...
PMID:Increase in length of experimental skin flaps that survive with dibutyryl cyclic AMP. 756 8

The possibility that pituitary adenylyl cyclase-activating peptide (PACAP) is an inhibitory neurotransmitter has been investigated in the taenia of the guinea-pig caecum. The action of PACAP on muscle contractility and its ability to alter levels of adenosine-3':5'-cyclic monophosphate (cyclic AMP) and guanosine-3':5'-cyclic monophosphate (cyclic GMP) were investigated. PACAP-1-27 was an effective agonist, giving relaxations comparable in magnitude to isoproterenol; its EC50 was 3.4 x 10(-7) M. PACAP (10(-6) M) caused an almost two-fold increase in cyclic AMP levels; but the level of cyclic GMP was not affected. The relaxation caused by PACAP was slow in onset, with a latency of 5.8 +/- 0.8 s and reached a maximum at 9.1 +/- 1.1 s after onset. The relaxation was significantly reduced by apamin (10(-6) M) and suramin (10(-4) M) but was not reduced by tetrodotoxin (10(-7) M). Relaxation of the taenia coli caused by electrical stimulation of the inhibitory nerves was greatly reduced by apamin but only slightly reduced by suramin. PACAP-like immunoreactivity (-IR) was localised immunohistochemically in varicose nerve fibres within the taenia coli and in the underlying myenteric plexus and circular muscle. Approx. 50% of vasoactive intestinal peptide (VIP)-IR nerve fibres in the taenia also had immunoreactivity for PACAP; conversely, almost all PACAP-IR fibres were immunoreactive for VIP. PACAP-IR and substance P (SP)-IR were generally in separate fibres; only about 5% of SP-IR fibres were PACAP-IR. Radioimmunoassay revealed tissue concentrations of PACAP-1-27 and PACAP-1-38 of 1.0 +/- 0.1 and 2.1 +/- 0.3 (SEM) pmol/g wet weight of tissue, respectively. Material with PACAP-1-27 immunoreactivity co-eluted with authentic PACAP-1-27 on gel filtration chromatography, and PACAP-1-38 immunoreactivity also co-eluted with the authentic peptide. This study provides structural, chemical and pharmacological evidence that PACAP could be involved in inhibitory neurotransmission to the taenia coli of the guinea-pig caecum.
 ...
PMID:Histochemical, pharmacological, biochemical and chromatographic evidence that pituitary adenylyl cyclase activating peptide is involved in inhibitory neurotransmission in the taenia of the guinea-pig caecum. 771 25

A clonal cell line derived from rat renal mesangial cells was shown to express endogenous 5-hydroxytryptamine (serotonin, 5-HT) receptors that mediate inhibition of cyclic AMP accumulation. These receptors were characterized as being of the 5-HT1B receptor subtype. 5-HT1 receptor agonists inhibited forskolin-stimulated cyclic AMP accumulation in rat renal mesangial cells (60-70% maximal inhibition) with the following rank order of potency (mean pEC50 values +/- SEM, n > or = 3): ergotamine (9.58 +/- 0.51) > RU 24969 (8.67 +/- 0.23) > or = 5-CT (8.42 +/- 0.06) > or = CP 93129 (8.15 +/- 0.27) > 5-HT (7.75 +/- 0.11) > sumatriptan (6.29 +/- 0.30) > 8-OH-DPAT (4.32 +/- 0.15). 5-HT2 and 5-HT4 receptor agonists were without effect. 5-HT-induced inhibition of cyclic AMP accumulation was abolished by a pre-treatment of the cells with pertussis toxin. (-)Propranolol was a partial agonist (27% maximal inhibition, pEC50 7.19 +/- 0.24, n = 3); when used as an antagonist at 1 microM, it shifted the concentration-response curve of 5-HT to the right (pKB 7.22 +/- 0.35, n = 3). Methiothepin was a competitive antagonist of 5-HT (pA2 8.04 +/- 0.10, Schild slope 0.87 +/- 0.21, n = 3). Rauwolscine (10 microM) had no antagonist activity. There was a significant correlation (r = 0.98, P = 0.0001) between the cyclic AMP data obtained in rat mesangial cells and 5-HT1B binding data reported in rat brain cortex. The same pattern of responses was observed in early passages of primary cultures of rat mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:5-Hydroxytryptamine 5-HT1B receptors inhibiting cyclic AMP accumulation in rat renal mesangial cells. 771 39

To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: -29 +/- 2% [SEM]; P < .01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P < .05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P < .05). Adrenomedullin decreased renal vascular resistance (10(-7) mol/L adrenomedullin: -41 +/- 2%; P < .001) and increased release of nitric oxide (+5.1 +/- 0.7 fmol/min per gram kidney weight; P < .001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor NG-monomethyl-L-arginine, and it also reversed the decrease in renal vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10(-7) mol/L adrenomedullin: +0.8 +/- 0.2 fmol/min per gram kidney weight; P < .01 versus control) and renal vasodilation (-28 +/- 6%; P < .05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P < .05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.
 ...
PMID:Mechanisms of adrenomedullin-induced vasodilation in the rat kidney. 772 34

In the present study, we examined the effect of pretreatment with VIP and various peptides structurally related to VIP such us PHI, helodermin, and secretin on VIP receptor number and affinity, as well as VIP-stimulated cyclic AMP production in rat peritoneal macrophages. Short-term (5-30 min) exposures of rat peritoneal macrophages to 0.1 microM VIP induced a rapid reduction in specific binding. Pretreatment for 15 and 30 min caused 26% (SEM = 6) and 48% (SEM = 4) reduction in specific binding, respectively. The maximal effect was observed at 120 min, causing a decrease of 67% (SEM = 6) in specific binding. Pretreatment with 0.1 microM VIP for 15, 30, and 120 min caused 23% (SEM = 9), 52% (SEM = 4), and 76% (SEM = 4) reduction in cyclic AMP production, respectively. Only VIP concentrations at the nanomolar level and higher were shown to be effective. The potency of VIP and related peptides to desensitize was similar to their potency to occupy receptors and to activate cyclic AMP production. The internalization of radioiodinated VIP was also studied. It was shown that receptor-bound ligand is internalized during the downregulation process. However, the diminution in VIP binding to macrophages was not completely explained by internalization.
 ...
PMID:Homologous regulation of vasoactive intestinal peptide (VIP) receptors on rat peritoneal macrophages. 778 61

cAMP is commonly measured using either immunoassay or high-performance liquid chromatography. The current methods are sensitive but may lack versatility and be expensive; also, radioactivity is potentially harmful to the operator and environment. Given these concerns, we developed a highly sensitive enzymatic fluorometric assay for cAMP. The method consists of five steps: (1) destruction of interfering compounds with apyrase, 5' nucleotidase, adenosine deaminase, and alkaline phosphatase; (2) conversion of cAMP to AMP; (3) conversion of AMP to ATP; (4) amplification of ATP by ATP-ADP cycling; and (5) fluorometric measurement of resultant NADPH. cAMP was measured in male Sprague Dawley rats anesthetized with pentobarbital. Stimulated rats (n = 4) received isoproterenol (16 micrograms/kg, s.q.) and aminophylline (20 mg/kg, s.q.), whereas controls (n = 4) received no additional drug. With the enzymatic fluorometric assay, cAMP content in heart, liver, and kidney (pmol/mg wet wt, mean +/- SEM) was 0.34 +/- 0.03, 0.33 +/- 0.03, and 0.92 +/- 0.11 in the control group and 0.77 +/- 0.10, 0.66 +/- 0.04, and 1.53 +/- 0.12 in the stimulated group, respectively. The total assay duration including sample reading procedure varied at 4.5-9.5 hr, depending on its sensitivity. cAMP from the same samples was measured using a commercially available enzyme immunoassay kit and was found to be very similar to the enzymatic fluorometric assay. We conclude that this new assay is sensitive, safe, versatile, and inexpensive and can be used to measure cAMP in multiple types of tissue, including biopsy samples weighing < 200 micrograms.
 ...
PMID:Enzymatic fluorometric assay for tissue cAMP. 786 85

Differences in purine metabolism produced by three preservation solutions were studied by determining the adenine nucleotide (ATP, ADP, AMP, and IMP) and nucleoside (adenosine, inosine, and hypoxanthine) levels in human kidney cortical biopsies. Forty kidney allografts were studied using University of Wisconsin (UW) solution (n = 20), Euro-Collins (EC) solution (n = 12), and modified EC solution with mannitol (M; n = 8). No significant differences were found between the three solutions studied with regard to ATP, ADP, or AMP changes. The mean ATP level (nmol/mg prot +/- SEM) at the end of preservation in the UW group was 2.7 +/- 0.3 nmol/mg, in the EC group 3.8 +/- 0.7 nmol/mg, and in the M group 2.3 +/- 0.4 nmol/mg. ATP 30 min after reperfusion in the UW, EC, and M groups was 5.7 +/- 0.8 nmol/mg, 6.4 +/- 1.0 nmol/mg, and 4.6 +/- 0.5 nmol/mg, respectively. However, an important difference appeared in the catabolic products determined. Kidneys perfused with UW solution had a significantly higher level of adenosine (2.6 +/- 0.6 nmol/mg), inosine (11.8 +/- 2.2 nmol/mg), and hypoxanthine (18.1 +/- 2.1 nmol/mg) at the end of cold storage than those perfused with EC (0.4 +/- 0.1 nmol/mg, 2.0 +/- 0.8 nmol/mg, and 7.1 +/- 1.4 nmol/mg) and M solutions (0.2 +/- 0.05 nmol/mg, 0.5 +/- 0.1 nmol/mg, and 5.2 +/- 0.6 nmol/mg; P < 0.05). These levels returned to initial values 30 min postreperfusion and there were no differences with the EC or M solution groups at that time.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of different preservation solutions on adenine nucleotide content and metabolism in human kidney transplantation. 817 10

We studied the influence of circulating parathyroid hormone-related protein (PTHrP) concentrations on the response of hypercalcemic cancer patients to bisphosphonate therapy. We also examined the changes in circulating PTHrP levels during the normalization of serum Ca to determine if part of the increase in PTHrP concentrations is not secondary to hypercalcemia itself, as suggested by some in vitro data. We sequentially measured in 45 hypercalcemic cancer patients treated by pamidronate the circulating concentrations of PTHrP (by an amino-terminal RIA; normal values < 9 pmol/liter), Ca, Ca2+, Pi, intact PTH, and the fasting urinary excretion of Ca (Ca/Cr) and cyclic AMP (cAMP). Mean +/- SEM baseline PTHrP levels were 9.5 +/- 1.3, with a median (range) value of 6.0 (< 3.4-43) pmol/liter. PTHrP levels were elevated in 18 of 45 patients, more often in epidermoid than in glandular carcinomas (P < 0.05), and they were significantly (P < 0.05) correlated with the concentrations of Pi (r = -0.46), Ca/Cr (r = -0.31), and urinary cAMP (r = 0.47). Mean pretreatment Ca levels were not significantly different between patients with elevated and patients with normal PTHrP levels, 13.3 +/- 0.4 versus 12.9 +/- 0.4 mg/dl, but the concentrations became significantly different (P < 0.005) 4 days after therapy, 10.2 +/- 0.3 versus 9.2 +/- 0.1 mg/dl, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Circulating PTHrP concentrations in tumor-induced hypercalcemia: influence on the response to bisphosphonate and changes after therapy. 832 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>