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Biomedical subjects

R L Singhal

Publications and source records attributed to R L Singhal.

At least 127 records · Page 7Linked to original sources
PubMed1975

Effect of radio-thyroidectomy and thyroid hormone replacement therapy on cardiac protein kinase activity and ATP hydrolysis.

The regulatory effect of thyroid hormone on cardiac protein kinase activity and ATP hydrolysis was studied in developing rats. Experimental hypothyroidism induced by a single intraperitoneal injection of 200 muCi of 131I led to a significant impairment of body and heart growth and elevated the activity of membrane-bound protein kinase (measured in the absence of cyclic AMP). However, a slight (11%) but statistically non-significant decrease was observed in soluble protein kinase activity in hearts of hypothyroid rats. Furthermore, thyroid deficiency produced in neonatal life significantly decreased (34%) the rate of cardiac ATP hydrolysis. Treatment of thyroidectomized animals with L-triiodothyronine initiated early in life produced a time-dependent increase in heart weight as well as the activity of soluble protein kinase and the rate of ATP hydrolysis in cardiac tissue. Maximal rise in these parameters was observed in hypothyroid rats receiving L-triiodothyronine treatment for 24 days beginning from 7 days after radioiodine injection. These animals also showed a marked cardiac hypertrophy. In contrast, replacement therapy with L-triiodothyronine produced a decrease in the activity of the membrane-bound protein kinase, which seemed to be inversely proportional to the duration of L-triiodothyronine treatment. Our data provide evidence suggesting that thyroid hormone plays an important role in controlling ATP turnover in hearts of developing rats.

Adenosine Triphosphate↗
PubMed1975

Protective effect of selenium on certain hepatotoxic and pancreotoxic manifestations of subacute cadmium administration.

Administration of cadmium chloride (1.0 mg/kg s.c.) to rats, twice a day for 7 days, significantly stimulated the activities of hepatic pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase, markedly increased the concentration of hepatic cyclic adenosine monophosphate and circulating blood glucose and significantly reduced serum insulin levels. Furthermore, subacute exposure to cadmium induced glucose intolerance that was associated with a decreased pancreatic secretory activity as evidenced by lowered insulinogenic indices and marked inhibition of phentolamine-stimulated insulin release. In contrast to cadmium, administration of selenium dioxide (2 X 1.0 mg/kg/day s.c., 7 days) failed to alter significantly the activities of gluconeogenic enzymes, hepatic cyclic adenosine monophosphate, blood glucose or serum insulin levels, glucose tolerance or the pancreatic secretory activity. However, administration of selenium concurrently with cadmium completely prevented the cadmium-induced increases of hepatic gluconeogenic enzymes. Treatment with selenium ameliorated the cadmium-induced hyperglycemia, hypoinsulinemia, glucose intolerance and the suppression of pancreatic secretory activity, whereas it failed to alter significantly the cadmium-induced elevation of hepatic cyclic AMP levels. Data provide evidence suggesting that subacute exposure to cadmium alters several parameters of carbohydrate metabolism and suppresses pancreatic secretory activity and that administration of selenium alone is without any appreciable effect on the above parameters. However, administration of selenium concurrently with cadmium prevents, to varying degrees, several of the cadmium-induced metabolic and functional changes.

Animals↗
PubMed1974

Persistence of cadmium-induced metabolic changes in liver and kidney.

Daily intraperitoneal injection of cadmium chloride (1 milligram per kilogram) for 45 days enhanced gluconeogenesis as evidenced by significant increases in the activities of liver and kidney cortex pyruvate carboxylase, phosphopyruvate carboxylase, hexosediphosphatase, and glucose-6-phosphatase, the quartet of key, rate-limiting enzymes involved in the biotransformation of noncarbohydrate precursors into glucose. Whereas cadmium treatment decreased the level of hepatic glycogen, the concentration of blood glucose and urea was significantly elevated by this heavy metal. Discontinuation of the heavy metal treatment for 28 days, in rats previously injected with cadmium for 45 days, failed to restore the observed biochemical alterations in hepatic and renal carbohydrate metabolism to control values. Evidence indicates that cadmium augments the glucose-synthesizing capacity of liver and kidney cortex and that various metabolic changes persist even after a 4-week period of withdrawal from exposure to the heavy metal.

Animals↗
PubMed1974

Role of cyclic adenosine 3':5'-monophosphate in the action of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT)on hepatic and renal metabolism.

The possibility whether alterations in the cyclic AMP-adenylate cyclase-phosphodiesterase system play a role in the action of 1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane (DDT) on hepatic and renal carbohydrate metabolism was investigated. Administration of exogenous cyclic AMP (10mg/100g) was found to mimic the action of DDT which enhanced the activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase, fructose 1,6-diphosphatase and glucose 6-phosphatase in both liver and kidney cortex, elevated the concentration of blood glucose and urea and decreased the amount of hepatic glycogen. Treatment with theophylline augmented the effects of a submaximal dose of this halogenated hydrocarbon on serum urea and glucose as well as the key gluconeogenic enzymes in liver and kidney cortex. Addition of DDT in vitro to liver and kidney homogenates resulted in a significant enhancement of adenylate cyclase activity. Hepatic and renal slices from rats already treated with DDT displayed an increased ability to convert [(3)H]adenosine into cyclic [(3)H]AMP. Whereas kidney-cortex slices excised from rats given caffeine and DDT produced an even greater amount of cyclic [(3)H]AMP, imidazole, propranolol and hydrazine prevented the insecticide-stimulated rise in cyclic nucleotide production. In contrast, prostaglandin E(1) failed to exert any significant effect on DDT-induced increases in cyclic [(3)H]AMP synthesis from radioactive adenosine. The present study and our previous findings (Kacew & Singhal, 1973e) support the concept that the DDT-induced alterations in carbohydrate metabolism of liver and kidney cortex may be related to an initial stimulation of the cyclic AMP-adenylate cyclase system in these tissues.

Adenosine↗
PubMed1974

A study of 3':5'-cyclic mononucleotide-dependent protein kinase from canine prostate glands.

1. An adenosine 3':5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase, located predominantly in the cytosol, was studied in canine prostate. 2. The enzyme exhibited cyclic AMP-binding activity, and could be isolated by chromatography on diethylaminoethyl cellulose. 3. The enzyme was maximally stimulated (fourfold) by 1mum-cyclic AMP, and half-maximal activation of the enzyme was observed in presence of 50nm-cyclic AMP. 4. Equilibrium studies at pH5.0 indicated the presence of one major class of binding site for cyclic AMP, with an association constant of approx. 10(8)m(-1). 5. Stimulation of the enzyme was also observed with the 3':5'-cyclic monophosphate derivatives of cytidine, inosine, guanosine and uridine as well as with dibutyryl cyclic AMP, but higher concentrations of these cyclic nucleotides were required to provide the same degree of activation as that seen with cyclic AMP. 6. Comparing alpha-casein, protamine and different histone subfractions as substrates, highest cyclic AMP stimulation was demonstrated with histones. 7. Although maximum velocity of the enzyme was enhanced approximately fivefold in presence of cyclic AMP, kinetic studies indicated that the apparent K(m) for histone (0.5mg/ml) remained the same whether determined in the presence or absence of the cyclic nucleotide. 8. In addition, cyclic AMP did not significantly change the apparent K(m) for ATP (1.2x10(-5)m). 9. The purified enzyme showed an absolute requirement for bivalent metal ion. Substitution of Mn(2+) for Mg(2+) decreased basal protein kinase activity as well as the stimulation noted with cyclic AMP. Similarly, the basal activity was lowered when Mg(2+) was replaced by Ca(2+) and cyclic AMP produced only little stimulation of the prostatic enzyme.

Adenosine Triphosphate↗