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Biomedical subjects

G Krishna

Publications and source records attributed to G Krishna.

At least 145 records · Page 8Linked to original sources
PubMed1980

Comparison of the biotransformation and hepatotoxicity of halothane and deuterated halothane.

To investigate the effect of deuterium substitution on the biotransformation and hepatotoxicity of halothane, male, phenobarbital-pretreated rats were exposed for 2 hr to 1% halothane or deuterated halothane (d-halothane) delivered in 14% O2-85% N2. The exposures were performed at mildly hypoxic conditions (14% O2) since it was previously established that the decreased oxygen tension promotes both the reductive metabolism of halothane and halothane-induced liver injury. At the end of anesthesia or at 24 hr, the rats were sarificed so that blood, liver and urine samples could be obtained for measurement of metabolites and assessment of liver damage. Deuterium substitution did not affect the levels of reductive metabolites of halothane (fluoride, CF3CH2Cl and CF2CHCl) nor did it alter the degree of hepatotoxicity as assessed by serum glutamic-pyruvic transaminase levels and morphological examination. The levels of oxidative metabolites (CF3COOH and bromide) were significantly reduced at the end of anesthesia and at 24 hr. It is concluded that halothane-induced hepatotoxicity is initiated by reactive intermediates formed during its reductive metabolism and that cleavage of the C-H bond is not involved in this pathway. The oxidative biotransformation of halothane proceeds by an oxygen insertion reaction at the C-H bond. Thus, the increased stability of the C-D bond explains the reduction in oxidative metabolities observed after exposure to d-halothane.

Animals↗
PubMed1978

A possible role for guanosine 3',5'-monophosphate in the stimulus-secretion coupling in exocrine pancreas.

Carbamylcholine, caerulein and cholecystokinin octapeptide rapidly increased the cyclic GMP concentration and amylase secretion in isolated guinea pig pancreatic slices. The cyclic GMP concentration was increased eight-fold over the basal concentration in 30 s, with concomitant increase in the rate of amylase secretion. The tissue concentration of cyclic GMP then rapidly declined to a plateau value of approx. 16% of the peak level within 10 min and was maintained at that concentration for the duration of the experiment. We have shown earlier (Kapoor, CL. and Krishna, G. (1977) Science 196, 1003--1005) that the decrease of tissue cyclic GMP was due mainly to the secretion of cyclic GMP into the medium. The cyclic AMP concentration in the tissue was not changed, nor was it secreted into the medium. There was a correlation between the concentration response to various agents for the increase in cyclic GMP concentration and amylase secretion in pancreatic slices. Carbamylcholine increased both the cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 1.5 micrometer concentration. Caerulein and cholecystokinin octapeptide were 5000 times more potent than carbamylcholine in increasing cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 0.3 nM concentration. Atropine, which completely inhibited the increase in cyclic GMP and amylase secretion induced by carbamylcholine, did not block the effects of caerulein or cholecystokinin octapeptide. These results suggest that various secretagogues induced amylase secretion by increasing the cyclic GMP concentration, but the mechanism by which cyclic GMP caused amylase secretion remains to be elucidated.

Amylases↗
PubMed1978

Characterization of guanylate cyclase of rod outer segments of the bovine retina.

Guanylate cyclase (GTP pyrophosphate-lyse (cyclizing), EC 4.6.1.2.) of bovine retinal rod outer segments is almost completely particulate, i.e. associated with rod outer segment membranes. In contrast to particulate guanylate cyclase in other tissues, treatment of rod outer segments with Triton X-100 does not solublize the enzyme but inhibits it. Enzyme activity is dependent on the presence of divalent cation, especially Mn2+ with only poor activation by Mg2+ (10-fold lower) and no activation seen with other cation. Ezpression of maximal activity required Nm2+ and GTP in equimolar concentrations with an apparent Km of 8 . 10(-4) M and V of 10 nmol/min per mg protein. Excess of Mn2+ over that required for the formation of the Mn . GTP complex was inhibitory. Ca2+, Ba2+ and Co2+ inhibited enzyme activity when assayed with the Mn . GTP substrate complex. In the presence of a fixed concentration of 1mM Mn2+, the enzyme exhibited strong negative cooperative interactions with GTP, characterized by an intermediary plateau region in the substrate vs. enzyme activity curve, a curve of downward concavity in the double reciprocal plot and a Hill coefficient of 0.5. Nucleotides such as ITP, ATP and UTP at higher concentrations (1 mM) stimulates activity by 40%. NaN3 has no effect on the guanylate cyclase. It is thus possible that the guanylate cyclase may be regulated in vivo by both the metal : GTP substrate ratio and the free divalent cation concentration as well as by the ATP concentration and thus play an important but yet undefined role in the visual process.

Animals↗
PubMed1978

Pineal serotonin N-acetyltransferase activity: abrupt decrease in adenosine 3',5'-monophosphate may be signal for "turnoff".

Dispersed pinealocytes have been used to study the role of adenosine 3',5'-monophosphate (cyclic AMP) in the "turnoff" of N-acetyltransferace activity. Activity was first stimulated 100-fold by treating cells with 1-norepinephrine. 1-Propranolol acted stereospecifically to rapidly reverse this, resulting in a 70 percent loss of enzyme activity within 15 minutes. An even more rapid 1-propranolol-induced decreased in cyclic AMP also occurred. This together with the observation that the inhibitory effect of 1-propranolol on N-acetyltransferase was blocked by dibutyryl cyclic AMP and phosphodiesterase inhibitors indicate that an abrupt decrease in cyclic AMP may be the signal for the rapid decrease in pineal N-acetyltransferase activity.

Acetyltransferases↗
PubMed1978

The effects of paraquat on prostaglandin synthesis of guinea pig lungs.

The effects of paraquat treatment (10 mg/kg i.p.) on the prostaglandin synthesizing ability of guinea pig lungs were examined in the present study. It was observed that paraquat-treated animals, as compared to controls, had a significantly reduced ability to synthesize PGF2 alpha and "PGE2" at 24 and 48 h after the treatment. Paraquat, however, failed to have any effect on prostaglandin synthesis in vitro. A decrease in the ability of prostaglandin synthesis in paraquat-treated guinea pig lung was attributed possibly to a decrease in the amount of lung microsomal protein.

Animals↗