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)

The effect of E-series prostaglandins (PGE) on hormone-stimulated glycogenolysis was studied in isolated rat hepatocytes. As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis. This effect could be reproduced by repetitive addition of PGE2 to compensate for PGE2 catabolism. In contrast, glycogenolysis stimulated by N6,O2'-dibutyryladenosine-3',5'-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 microM dibutyryl-cAMP plus 1.7 microM 16,16-dimethyl-PGE2 = 99 +/- 6% of rate with 0.34 microM dibutyryl-cAMP alone; mean +/- SEM, N = 5). Similarly, glycogenolysis stimulated by 8-bromoadenosine-3',5'-cyclic monophosphate was not inhibited by PGE2 or 16,16-dimethyl-PGE2. Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner. PGE inhibited the cAMP-independent stimulation of glycogenolysis resulting from phenylephrine or angiotensin II exposure (rate of glycogenolysis with 8 microM phenylephrine + 1.7 microM 16,16-dimethyl-PGE2 = 65 +/- 10% of rate with 8 microM phenylephrine alone, N = 4, P less than 0.05; 4.9 microM angiotensin II + 1.7 microM 16,16-dimethyl-PGE2 = 75 +/- 7% of rate with 4.9 microM angiotensin II alone, N = 4, P less than 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 micrograms/ml A23187 + 1.7 microM 16,16-dimethyl-PGE2 = 83 +/- 5% of rate with 0.55 micrograms/ml A23187 alone, N = 7, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of E-series prostaglandins on cyclic AMP-dependent and -independent hormone-stimulated glycogenolysis in hepatocytes. 298 82

Thyrotropin (TSH), stimulators of guanyl nucleotide regulatory protein, (sodium fluoride and guanyl-5'-yl-imido-diphosphate [Gpp(NH)p]) and a stimulator of the catalytic unit of adenylate cyclase (AC) (forskolin) were used to probe the TSH receptor-guanyl nucleotide regulatory protein-cyclase unit in normal and neoplastic thyroid tissue from 17 patients. Eleven of these patients had benign follicular adenomas and six patients had differentiated thyroid carcinomas. An 8000 X g particulate fraction that is rich in thyroid plasma membranes was prepared, and the activity of AC was determined by the conversion of alpha-32P-ATP to P32-cAMP. Thyroid neoplasms had a greater AC response to TSH than did normal thyroid tissue removed from the same patients (p less than 0.001). The AC response to NaF and Gpp(NH)p was greater in the neoplastic thyroid tissue, although in these experiments the increase was not significant. In contrast, the AC response to forskolin was comparable in normal (573 +/- 129) and neoplastic (526 +/- 132) thyroid tissue (mean +/- SEM). The effects of NaF, Gpp(NH)p, and forskolin on AC activity were additive with TSH when used at concentrations for optimal AC activity. Low concentrations of NaF and Gpp(NH)p stimulated AC activity whereas high concentrations of NaF and Gpp(NH)p assayed either together or separately inhibited AC activity. When forskolin and NaF were assayed together there was a greater than additive effect or potentiated effect on activity. Basal AC activity was increased in the presence of manganese (Mn+2) (2 mM) over magnesium (Mg+2) (2 mM) (p less than 0.001), whereas TSH-stimulated (p less than 0.01) and Gpp(NH)p-stimulated AC activity (p less than 0.05) were lower in the presence of Mn+2 than Mg+2. There was an excellent correlation between basal AC activity and AC activity in response to forskolin in both normal and neoplastic thyroid tissue, whereas there was no correlation between basal AC activity and TSH-stimulated AC activity in the thyroid neoplasms. These data suggest that the abnormality responsible for the greater AC response to TSH in neoplastic thyroid tissue is proximal to the catalytic unit of AC and most probably is due to an alteration in the guanyl nucleotide regulatory protein or in the coupling of the guanyl nucleotide regulatory protein to either the receptor or the catalytic unit of AC.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Thyrotropin regulation of adenylate cyclase activity in human thyroid neoplasms. 298 5

Rat reticulocytes contain a cytosol activator protein (RCAP) that augments catecholamine-sensitive adenylate cyclase activity in reticulocyte membranes. A highly purified preparation of RCAP, obtained by Sephacryl S-200 chromatography, was used to elucidate further its mechanism of action. The specific activity of the S-200 fraction to augment isoproterenol responsiveness was increased approximately 1,100-fold over the starting material, from 1.2 to 1,300 nmol cAMP formed per mg RCAP. The mol wt of RCAP is approximately 20,000. The effect of RCAP to enhance isoproterenol responsiveness was apparent within 20 sec, virtually abolishing the normal lag time of hormone-activated adenylate cyclase. In addition to its effects on catecholamine-responsive adenylate cyclase, RCAP significantly increased basal [21 +/- 3 (+/- SEM) to 41 +/- 4 pmol/mg protein X 30 min; P less than 0.02], guanyl-5'-yl-imidodiphosphate-associated (3173 +/- 213 to 4339 +/- 365 pmol/mg X 30 min; P less than 0.03), and fluoride-associated (5152 +/- 64 to 5807 +/- 58 pmol/mg X 30 min; P less than 0.05) adenylate cyclase activities. RCAP also altered the characteristics of agonist binding to the beta-adrenergic receptor of reticulocyte membranes, causing an increase in the apparent IC50 for isoproterenol from 0.7 +/- 0.2 to 7.9 +/- 1.6 microM (P less than 0.001). Similar to its effects on reticulocytes, RCAP enhanced isoproterenol- and prostaglandin E2-sensitive adenylate cyclase activity in the wild-type S49 lymphoma cell and shifted the binding isotherm for isoproterenol rightward. In cyc-, the mutant that lacks the stimulatory guanine nucleotide-binding protein (Ns) and in UNC, the mutant in which receptors are uncoupled from N, RCAP was ineffective. Moreover, RCAP decreased agonist affinity for the beta-adrenergic receptor in wild-type S49 cells, but not in cyc- or UNC cells. These observations suggest that RCAP requires a functional Ns unit for its effects on hormone-sensitive adenylate cyclase activity.
 ...
PMID:Cytosol activator protein from rat reticulocytes requires the stimulatory guanine nucleotide-binding protein for its actions on adenylate cyclase. 298 18

A polyuric syndrome with nephrogenic diabetes insipidus (NDI) is a frequent consequence of prolonged administration of lithium (Li) salts. Studies in the past, mainly the acute and in vitro experiments, indicated that Li ions can inhibit hydroosmotic effect of [8-arginine]vasopressin (AVP) at the step of cAMP generation in vitro. However, the pathogenesis of the NDI due to chronic oral administration of low therapeutic doses of Li salts is not yet clarified. We conducted a comprehensive study to clarify the mechanism by which Li administered orally for several weeks induces polyuria and NDI in rats. Albino rats consuming a diet which contained Li (60 mmol/kg) for 4 wk developed marked polyuria and polydipsia; at the end of 4 wk the plasma Li was 0.7 +/- 0.09 mM (mean +/- SEM; n = 36). Li-treated rats had a significantly decreased (-33%) tissue osmolality in papilla and greatly reduced cortico-papillary gradient of urea (cortex--43%; medulla--64%; papilla--74%). Plasma urea was significantly (P less than 0.001) lower in Li-treated rats (5.4 +/- 0.2 mM) compared with controls (6.8 +/- 0.3 mM). Medullary collecting tubules (MCT) and papillary collecting ducts (PCD) microdissected from Li-treated animals had higher content of protein than MCT and PCD from the control rats. The cAMP accumulation in response to AVP added in vitro was significantly (delta = -60%) reduced. Also, the cAMP accumulation in MCT and PCD after incubation with forskolin was markedly lower in Li-treated rats. Addition of 0.5 mM 1-methyl,3-isobutyl-xanthine did not restore the cAMP accumulation in response to AVP and forskolin in MCT from Li-treated animals. In collecting tubule segments from polyuric rats with hypothalamic diabetes insipidus (Brattleboro homozygotes) the AVP-dependent cAMP accumulation was not diminished. The activity of adenylate cyclase (AdC) in MCT of Li-treated rats, both the basal and the activity stimulated by AVP, forskolin, or fluoride, was significantly (delta approximately equal to -30%) reduced, while the activity of cAMP phosphodiesterase (cAMP-PDIE) in the same segment showed no significant difference from the controls. Also, the content of ATP in MCT microdissected from Li-treated rats and incubated in vitro did not differ from controls. The rate of [14C]succinate oxidation to 14CO2 in MAL was inhibited (-77%) by 1 mM furosemide, which indicates that this metabolic process is coupled with NaCl cotransport in MAL. The rate of (14)CO(2) production from [14C]succinate in MAL was not significantly different between control and Li-treated rats. In MCT of control rats, the rate of [14C]succinate oxidation was approximately 3 times lower than in MAL. The rate of (14)CO(2) production from [(14)C]succinate in MCT of Li-treated rats was significantly (delta +33%) higher than in MCT dissected from control rats. Based on these results, we conclude that at least two factors play an important role in the pathogenesis of NDI consequent to chronic oral administration of Li: (a) decreased ability of MCT and PCD to generate and accumulate cAMP in response to stimulation by AVP; this defect is primarily due to diminished activity of AdC in these tubular segments caused by prolonged exposure to Li; and (b) lower osmolality of renal papillary tissue, due to primarily to depletion of urea, which decreases osmotic driving force for water reabsorption in collecting tubules. On the other hand, NaCI reabsorption in MAL is apparently not affected by chronic Li treatment.
 ...
PMID:Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats. 298 35

In the present study we have demonstrated that human peripheral blood granulocytes from elderly subjects exhibit reduced chemotaxis and degranulation in response to stimulation with fMet-Leu-Phe. Cyclic AMP levels in non-stimulated cells were not significantly different (mean +/- SEM): 4.8 +/- 0.6 and 3.9 +/- 0.4 pmol/10(7) cells for young and elderly respectively. Stimulation with fMet-Leu-Phe (5 X 10(-7) mol/l) for 30s induced the production of cyclic AMP: 8.4 +/- 0.5 and 6.7 +/- 0.3 pmol/10(7) cells for young and elderly. These findings, together with those previously published by us, suggest that cyclic AMP production and cellular functions which this molecule participates in are reduced in cells from elderly individuals.
 ...
PMID:Age-related differences in granulocyte chemotaxis and degranulation. 300 6

The pattern of GH secretion undergoes substantial changes in the aging rat, resulting in decreased daily secretion of GH. In this study, the pituitary responsiveness to GH-releasing factor (GRF) was examined in young (2- to 5-month old) and aging (14- to 18-month old) male rats. In vivo studies were performed under sodium pentobarbital anesthesia. After injection of 250 ng GRF/100 g BW, young rats experienced more GH secretion [peak level, 544.5 +/- 209.5 (+/- SEM) ng/ml] than did 18-month-old rats (89.3 +/- 13.7 ng/ml). To investigate the locus of this insensitivity to GRF, anterior pituitary cells from young and aging rats were dispersed and placed in primary culture. While basal GH secretion from the cultured pituitary cells was similar in the two groups (49.7 +/- 3.5 vs. 47.8 +/- 2.7 ng/ml X 4 h for the 2- and 18-month old rats, respectively), the GH-releasing ability of GRF was partially but significantly impaired in cells derived from both 14- and 18-month old rats; 100 nM GRF stimulated the release of 96.7 +/- 1.8 ng/ml X 4 h in the 18-month old rats as opposed to 115.0 +/- 6.0 (P less than 0.05) ng/ml X 4 h in the 2-month-old rats. Since GRF stimulates GH release through the activation of adenylate cyclase, intracellular cAMP levels were measured in the cultured pituitary cells. GRF stimulated 65% less intracellular cAMP accumulation in the 18-month-old rats. In 14-month-old rats, the ability of forskolin and (Bu)2 cAMP to release GH was impaired, while phorbol ester-elicited GH secretion was unchanged. In conclusion, the GH response to GRF is blunted in aging rats. While much of the insensitivity to GRF may be mediated by the increased somatostatin tone reported in aging rats, a diminished pituitary cAMP response to GRF may also be an important etiological factor in the hyposomatotropinemia of the aging male rat.
 ...
PMID:Diminished pituitary responsiveness to growth hormone-releasing factor in aging male rats. 300 51

When grown as sc tumors in the nude (nu/nu) mouse, cells of the established human renal carcinoma cell line 786-0 produce hypercalcemia; this has an apparent humoral basis because it is reversed by resection of the primary tumor. We have investigated the pathogenesis of hypercalcemia in this model. Tumor-bearing mice were hypercalcemic (13.4 +/- 0.9 vs. 9.52 +/- 0.13 mg/dl in control mice) and hypophosphatemic (10.0 +/- 0.8 vs. 13.8 +/- 1.5 mg/dl in control mice; all values are mean +/- SEM). The serum concentration of 1,25-dihydroxyvitamin D was increased in tumor-bearing animals (70.0 +/- 9.3 vs. 43.8 +/- 4.8 pg/ml in control animals). Urinary excretion of cAMP was similar in control (33.7 +/- 1.4 nmol/mg creatinine) and tumor-bearing mice (38.2 +/- 4.7 nmol/mg creatinine). However, in the latter, the acute response of urinary cAMP to PTH was blunted. Although intestinal calcium transport in everted duodenal sacs in vitro was increased in tumor-bearing mice, hypercalcemia was unaffected by feeding the animals for 8 days a diet containing less than 0.02% calcium. Hence, absorption of dietary calcium did not play a significant role in maintenance of hypercalcemia. In hypercalcemic animals, the calcium content of the humerus was decreased (2.95 +/- 0.08 vs. 3.29 +/- 0.13 mg in controls; P less than 0.05). Quantitative histomorphometric analysis of the distal femoral metaphysis disclosed a significant reduction in trabecular bone volume in tumor-bearing mice (12.0 +/- 1.1% vs. 16.1 +/- 1.1% in controls; P less than 0.02). A strong trend for increased osteoclast surface and number was observed, suggesting that bone resorption was increased. Osteoblast surface and number were also somewhat increased, as was the rate of mineral apposition (2.55 +/- 0.14 vs. 1.91 +/- 0.04 micron/day in controls; P less than 0.01). Thus, the decrease in trabecular bone volume was associated with high turnover of bone, with an apparent net increase in bone resorption. We conclude that hypercalcemia in the nude mouse bearing human renal carcinoma cells is associated with increased bone resorption, high bone turnover, hypophosphatemia, and increased serum levels of 1,25-dihydroxyvitamin D.
 ...
PMID:Pathogenesis of hypercalcemia in nude mice bearing a human renal carcinoma. 301 91

We studied the regulation of beta-adrenergic receptors in human mononuclear leukocytes (MNL). Total receptor number was determined as specific binding at 4 C of [3H] dihydroalprenolol or [125I]iodopindolol, and redistributed receptors were defined as those binding sites to which the hydrophilic antagonist CGP-12177 did not have access. Receptor function was assessed as cAMP accumulation stimulated by isoproterenol. In in vitro experiments, high concentrations of isoproterenol desensitized receptor function and promoted redistribution of about 80% of the receptors away from the cell surface. However, three in vivo protocols (upright posture for 3 h, moderate exercise, and infusion of isoproterenol for 30 min) redistributed few beta-adrenergic receptors on MNL. The 30-min isoproterenol infusion did not alter later cAMP accumulation, but posture change and exercise increased isoproterenol-stimulated cAMP accumulation in intact MNL. Infusion of isoproterenol for 120 min redistributed 9 +/- 2% (+/- SEM) of the receptors and decreased isoproterenol-stimulated cAMP accumulation by 19 +/- 6%. Isoproterenol-stimulated adenylate cyclase activity in membranes isolated from MNL previously was found to be decreased with upright posture, and we confirmed these findings in assays that did not include exogenous GTP, but instead relied upon guanine nucleotides retained in the membrane preparation. However, when excess GTP was included, isoproterenol-stimulated adenylate cyclase activity in MNL membranes was not altered by posture change. We conclude that substantial receptor redistribution of beta-receptors on MNL does not readily occur in physiological situations.
 ...
PMID:In vivo regulation of beta-adrenergic receptors on human mononuclear leukocytes: assessment of receptor number, location, and function after posture change, exercise, and isoproterenol infusion. 301 26

Progesterone induces in vitro the meiotic cell division of Xenopus full-grown oocytes. Microinjection into oocyte of a solution containing Mg2+ (20 mM) facilitates by one order of magnitude the dose of progesterone which induces 50% of germinal vesicle breakdown. Microinjected in the absence of hormone, Mg2+ and also Mn2+ can induce maturation with efficiencies of, respectively, 24% (SEM = 8; n = 13) and 70% (SEM = 6; n = 23). The dose-response curves of cation-induction of maturation show an optimum of 20 mM for Mg2+ and 15 mM for Mn2+ (pipet concentration); higher doses were less active. Cation-induction of maturation is inhibited when oocytes are preincubated with cholera toxin (500 ng/ml); nevertheless, it cannot be interpreted at the level of cAMP, since both Mg2+ and Mn2+ microinjections provoke an increase in the oocyte cAMP content. Mg2+ induction of maturation is more efficient when oocytes are incubated in trimethylamine at pH 8.2, which is known to increase intracellular pH suggesting an action at the level of alkali pH-sensitive enzymes. Altogether, our results indicate a positive role for Mg2+ ions in the induction of oocyte maturation and raise an attractive hypothesis about the respective roles of cAMP and Mg2+ changes involved in the mechanism of progesterone action. Our results also show that co-injection of 2-glycerophosphate and Mg2+ ions, which are both commonly used in the preparation of the MPF mitotic factors from dividing cells, induces oocyte maturation more efficiently than Mg2+ alone and drastically shortens the kinetics of germinal vesicle breakdown to 1 h 30 min to 2 h 30 min.
 ...
PMID:A possible role for Mg2+ ions in the induction of meiotic maturation of Xenopus oocyte. 302 45

Plasma concentrations of cyclic nucleotides (cAMP, cGMP) were measured before and during bicycle exercise in 8 well-controlled (mean pre-exercise blood glucose 5.3 mmol/l; HbA1 8.6%) and 8 moderately controlled (mean pre-exercise blood glucose 12.2 mmol/l; HbA1 10.8%) patients aged 18-32 years with insulin-dependent diabetes mellitus (IDDM) and in a group of non-diabetic control subjects matched for age and sex. Pre-exercise plasma cAMP concentrations and the rise with exercise were similar in all study groups. Significantly lower resting cGMP levels were found in well-controlled IDDM patients (3.5 +/- 0.3 pmol/ml, mean +/- SEM) compared to controls (5.6 +/- 1.1 pmol/ml; p less than 0.05) and moderately controlled IDDM patients (5.6 +/- 1.0 pmol/ml; p less than 0.05). By contrast, plasma cGMP levels increased during exercise in the diabetics but not in the controls. These findings indicate a significant difference in responses of plasma cGMP to exercise between IDDM patients and controls.
 ...
PMID:Influence of metabolic control of insulin-dependent diabetes on plasma nucleotide levels (cAMP, cGMP) during bicycle exercise. 303 Jun 20


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