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Biomedical subjects

L A Barker

Publications and source records attributed to L A Barker.

17 recordsLinked to original sources
PubMed1992

Effect of short-term treatment with gastrin and related peptides on gastrointestinal histamine H2-receptors.

The effects of short-term, 7-day, treatment with synthetic 15-leucine human gastrin I, pentagastrin or sulfated cholecystokinin-8 on the activity of histamine (HA)-stimulated adenylate cyclase in membranes isolated from guinea pig gastric mucosa and H2-receptor-mediated contractions of isolated ilea were evaluated. Treatment with each of the peptides produced a decrease in the maximal rate of HA-stimulated adenylate cyclase. The decreases in the maximal rate occurred without any effect on the potency of HA or any effect on basal rates of activity. In animals treated with pentagastrin, but not with cholecystokinin octapeptide sulfate, the contractile activity of dimaprit, a selective H2-agonist, was decreased. In animals treated with pentagastrin, the contractile actions of pentagastrin on isolated ileal preparations were increased. A 7-day treatment with the H2-antagonist, tiotidine, did not alter the potency of or the maximal response for HA-stimulated adenylate cyclase activity. Co-treatment with tiotidine prevented the effects of pentagastrin on gastric mucosal HA-stimulated adenylate cyclase. Treatment with pentagastrin did not alter the sensitivity of the gastric mucosal H2-receptor to inhibition by tiotidine. The effects of treatment with gastrin on NaF-stimulated adenylate cyclase activity also were determined. Treatment with gastrin did not alter the actions of NaF, suggesting that the coupling between the Gs subunit and the catalytic subunit of adenylate cyclase was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1990

Supersensitivity and changes in the active population of beta adrenoceptors in rat right atria in early sepsis.

We have investigated the effect of sepsis induced by cecal ligation and puncture on the chronotropic actions of beta adrenoceptor agonists on isolated right atria. The present findings show that right atria obtained from rats in an early stage of sepsis were supersensitive to the chronotropic actions of the beta-agonists, isoproterenol (ISO), fenoterol (FEN) and prenalterol (PREN). The supersensitivity to the chronotropic actions of ISO and FEN was much greater than that which developed to PREN. The positive chronotropic actions of isobutylmethylxanthine and forskolin were not affected by sepsis. The receptor subtypes mediating the responses to ISO, FEN and PREN by control and septic right atria were characterized by functional assays using selective beta-1 and beta-2 antagonists. The results showed that the chronotropic response produced by all three agonists on right atria obtained from control rats were mediated by beta-1 receptors. In contrast, the chronotropic actions of ISO and FEN on atria from septic rats were mediated by what appears to be beta-2 receptors and those of PREN by beta-1 receptors.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Cardiac function and chronotropic sensitivity to beta-adrenergic stimulation in sepsis.

An organism's cardiovascular response to sepsis is at least partly dependent on hormonal and neural modulation of myocardial function. We have investigated both intrinsic myocardial performance and one aspect of myocardial sensitivity to beta-adrenergic stimulation in a model of sepsis in which animals, at the time studied, exhibited bacteremia, normal arterial blood pressure and cardiac output, elevated heart rate, and elevated plasma catecholamines. Intrinsic myocardial contractile function, studied with the isolated, perfused working heart preparation, was depressed over a range of preloads in septic animals, whereas heart rate was elevated. To determine whether hearts from septic animals could respond normally to beta-adrenergic stimulation, we studied chronotropic responses to isoproterenol in both Langendorff perfused hearts and in isolated right atria. In langendorff perfused hearts from septic animals, basal rates were significantly increased and lower concentrations of isoproterenol elicited greater increases in heart rate. In isolated right atria from septic animals, basal rates were also elevated and the EC50 for the chronotropic response to isoproterenol was significantly less than in atria from control animals. The maximal heart rate response to isoproterenol was not significantly different from control. These results indicate that in sepsis, despite apparently adequate in vivo cardiac performance, intrinsic myocardial function is depressed, but chronotropic sensitivity to beta-adrenergic stimulation is increased.

Animals↗
PubMed1986

Metronidazole and 5-aminosalicylic acid enhance the contractile activity of histaminergic agonists on the guinea-pig isolated ileum.

The effects of metronidazole and 5-aminosalicylic acid (5-ASA) on histamine receptor-effector systems in the small intestine and right atrium of the guinea pig were studied. In an apparently all-or-none manner, both caused a sinistral shift in dose-response curves for the phasic component of the contractile response to histamine at H1 receptors on the ileum. In the presence of either, the EC50 value for histamine was reduced from 0.07 to about 0.03 microM. Similarly, in an apparently all-or-none fashion, both produced an elevation in the dose-response curve for the actions of dimaprit at H2-receptors in the ileum; the response to all doses was increased about 30% with no significant change in the EC50 value. Metronidazole and 5-ASA did not alter dose-response curves for the tonic contractile response to histamine or curves generated by the cumulative addition of histamine. Also, neither altered the positive chronotropic response on isolated right atria or the phasic contractile response on isolated segments of jejunum and duodenum to histamine or dimaprit. Likewise, neither altered dose-response curves for the direct action of carbamylcholine at muscarinic receptors or for the indirect actions of dimethylphenylpiperazinium on the ileum. The effects of 5-ASA or metronidazole on the response to histamine could be prevented as well as reversed by scopolamine or tetrodotoxin. The results suggest that metronidazole and 5-ASA enhance the actions of histamine and dimaprit on the ileum by an action on myenteric plexus neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminosalicylic Acids↗
PubMed1985

Regional variation in the sensitivity of longitudinal smooth muscle to histamine at H1-receptors in guinea-pig ileum and colon.

The sensitivity of the distal ileum, proximal colon, medial colon, and distal colon of the guinea-pig to histamine has been evaluated. The rank order of sensitivity was ileum greater than medial colon greater than proximal colon approximately equal to distal colon. The mean -logEC50 values at receptors in the ileum, medial, proximal, and distal colon were 6.74, 6.18, 5.79, and 5.72, respectively. The apparent dissociation constant for the interaction of histamine with receptors in the various regions was determined. The -log Kd values at receptors in the ileum, proximal colon, medial colon, and distal colon were 4.68, 4.65, 4.62, and 4.44, respectively. The mean apparent -log Kd values for the antagonism of histamine by mepyramine were 9.0, 9.0, 9.1, and 8.9 for receptors on the ileum, proximal, medial, and distal colon, respectively. The results of these experiments provide no evidence that histamine receptors in the colon are distinguishable from H1-receptors as characterized on the ileum. The differences in sensitivity to histamine in the various regions of the intestine may be due to differences in the density of H1-receptors.

Animals↗
PubMed1978

Effect of sodium chloride on changing the rate-limiting step in the human placental choline acetyltransferase reaction.

The kinetic constants, Km and Vmax, for the choline acetyltransferase reaction were determined for choline and eight choline analogs under conditions of high (0.3 M) and low (approximately 0.01 M) sodium chloride. At high sodium chloride, the maximal velocities of the different substrates varied over 27-fold, while at low sodium chloride, less than a 5-fold variation was observed. Dead-end inhibition studies using acetylaminocholine as the inhibitor showed that under conditions of high sodium chloride, inhibition changes from noncompetitive to competitive as the reactivity of the substrate decreases. Under conditions of low sodium chloride, acetylaminocholine inhibition is nonlinear and noncompetitive with respect to all substrates tested. These results suggest that increased ionic strength increases the rate of coenzyme A dissociation from the enzyme. The rate-determining step of the reaction can be ternary complex interconversion, coenzyme A release, or both, depending on the ionic strength and the substrate employed.

Choline O-Acetyltransferase↗
PubMed1975

Comparative studies of substrates and inhibitors of choline transport and choline acetyltransferase.

Analogs of choline and three hemicholinium derivatives were studied as substrates for choline acetyltransferase (ChAc) and as substrates or inhibitors of the high-affinity choline transport system in rat brain synaptosomes. Hemicholiniums-3 and -15, but not terphenylhemicholinium-3, were substrates of ChAc. All three inhibit the high-affinity choline transport system, with I50 values of 0.08, 8.0 and 0.08 muM, respectively. Simple choline analogs with substituents on the beta-carbon atom were found to be very poor substrates for ChAc. N-alkyl analogs, mono-, di- and triethyl choline and N-hydroxyethyl pyrrolidinium methiodide (pyrrolcholine), and DL-alpha-methyl choline are substrates for ChAc and also inhibit choline transport, with I50 values between 2 to 6 muM.[3-H] choline, [3-H] monoethycholine and [3-H] pyrrolcholine were transported into synaptosomes by the choline high affinity system and metabolized to acetyl derivatives. The results indicated that choline transport is the rate-limiting step in the biosynthesis of acetylcholine and provide the basis for the development of a group of cholinergic false transmitters.

Acetyltransferases↗
PubMed1972

Choline metabolism in the cerebral cortex of guinea pigs. Stable-bound acetylcholine.

1. The turnover of synaptosomal (vesicular-cytoplasmic) and stable-bound (vesicular) acetylcholine isolated from cortical tissue was investigated after the administration, under local anaesthesia, of [N-Me-(3)H]choline into the lateral ventricles of guinea pigs. 2. Radioactive acetylcholine and choline present in acid extracts of subcellular fractions were separated by a combination of liquid and column ion-exchange and thin-layer chromatography. 3. The specific radioactivity and pattern of labelling of acetylcholine present in a fraction of monodisperse synaptic vesicles was found to be essentially the same as that of synaptosomal acetylcholine. 4. The specific radioactivity of stable-bound acetylcholine present in partially disrupted synaptosomes (fraction H) at short times (10-20min) after the injection of [N-Me-(3)H]choline was very variable and inversely related to the yield of acetylcholine in that fraction. 5. Evidence was found for the existence of two small, but highly labelled pools of acetylcholine, one which could be isolated in fraction H and the other which was lost when synaptosomes, after isolation by gradient centrifugation, were left at 0 degrees C or pelleted. 6. It is concluded that the results are best explained by metabolic differences among the nerve-ending compartments (thought to be vesicles) which contain stable-bound acetylcholine. Computer simulation of our experiments supports this possibility and suggests that the highly labelled pool in fraction H is present in vesicles close to the external membrane.

Acetylcholine↗
PubMed1972

Choline metabolism in the cerebral cortex of guinea pigs. Phosphorylcholine and lipid choline.

1. The labelling of phosphorylcholine and choline-containing phospholipids in the subcellular fractions of guinea-pig cerebral cortex after the intraventricular injection of [N-Me-(3)H]choline into conscious animals has been studied. Special emphasis was placed upon the synaptosome fraction and early time-periods after administration. 2. The labelling of phosphorylcholine was rapid compared with that of phospholipid and was confined to two distinct subcellular fractions: the soluble cytoplasmic fraction and the synaptosome fraction. Most of the labelled phosphorylcholine of the synaptosome fraction was readily released by osmotic rupture indicating location in the nerve-ending cytoplasm. The two pools of phosphorylcholine had similar specific radioactivities at all observed times. 3. (3)H-labelled phospholipid was found in all membranous fractions. The labelling was confined to choline-containing phospholipids, notably phosphatidylcholine. 4. The labelling of the different membranous fractions was similar. 5. The half-life of the choline-containing phospholipids in the synaptic vesicle fraction was very much greater than the acetylcholine in this fraction. 6. Evidence is presented that synthesis de novo of phosphatidylcholine at nerve terminals occurs in vivo.

Acetylcholine↗