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Biomedical subjects

W J Thompson

Publications and source records attributed to W J Thompson.

At least 163 records · Page 9Linked to original sources
PubMed1976

Hormonal regulation of pancreatic islet adenyl cyclase.

Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E1 (PGE1) and GTP. Isoproterenol activation was additive with PGE1, as was that of secretin with PGE1, but only in the presence of GTP. Secretin activation in the presence of PGE1 and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE1 and guanine nucleotide modulation of the adenyl cyclase activation process.

Adenylyl Cyclases↗
PubMed1976

Re-evaluation of the role of cyclic AMP in histamine-induced gastric acid secretion.

The 600 x g particulate fraction of gastric mucosal scrapings from rats was incubated with 3H-metiamide which saturated available binding sites at a concentration of 1 muM. Scatchard plots showed a single component with a Kd value of 0.2 muM. Unlabelled cimetidine and histamine competed with 3H-metiamide binding. The 600 x g particulate fraction also contained all of the hormone and sodium fluoride sensitive adenylyl cyclase. Adenylyl cyclase activity was not altered by histamine, pentagastrin or carbachol but was increased during incubation with prostaglandin E1, secretin and epinephrine. These findings do not support the hypthesis that gastric secretion is mediated by intracellular accumulation of cyclic AMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Cyclic AMP and gastric secretion: the illusive second messenger.

We have surveyed the literature which bears upon the contention that accumulation of intracellular cyclic AMP is a necessary intermediate event between secretagogue and secretion of acid by the stomach. In our view, the evidence in favor of this hypothesis is wanting for these three reasons: (i) the evidence does not fit with better established information about regulation of gastric secretion and about hormonal actions on the cyclic AMP system; (ii) technological problems involved in the biological preparations employed and in the assay procedures used make the evidence nearly uninterpretable; and (iii) there exists a body of contradictory evidence at least as convincing as that which favors the thesis. These three arguments against acceptance of the theory are not definitive and are not intended to dissuade investigators interested in gastric mucosal metabolism from their quest. And, although we are not at this time adherents of the preceding hypothesis, we are also not unmindful of its basic appeal, which has attracted numerous scientists into a study of the metabolic correlates of gastric acid secretion. Unfortunately the general appeal of the second messenger hypothesis is such as to make it almost a paradigm of gastric secretory physiology in the seventies, in Kuhn's sense of that word (118). The disadvantages of paradigms are that they tend to obscure negative evidence among their adherents, and they arouse controversies more marked by heat than by light.

Animals↗
PubMed1975

Isolation of an activator of multiple forms of cyclic nucleotides phosphodiesterase of rat cerebrum by isoelectric focusing.

An isoelectric focusing technique was used to isolate multiple forms of cyclic nucleotide phosphodiesterase from a 105 000 times g soluble supernatant fraction of sonicated rat cerebrum. These separated peaks of activity had iso-electric points of 5.1, 5.6, 6.0, 6.6, 8.0, and 9.0. The activities were not stimulated by an endogenous activator of the enzyme but were inhibited by EGTA treatment. However, activator-sensitive forms of the enzyme could be separated from brain if the preparation of rat cerebrum was dialyzed against an EGTA containing buffer prior to electrofocusing. The procedure was also used to isolate a column fraction that stimulated maximum velocities of cyclic AMP and cyclic GMP hydrolysis. This fraction was itself devoid of phosphodiesterase activity and had an isoelectric point of 4.7.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1975

Cyclic nucleotide phosphodiesterases and thyroid hormones.

Evidence is presented that modulation of the maximum velocity of a particulate low K-m cyclic adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase by thyroid hormones is one mechanism for the regulation of the responsiveness of rat epididymal adipocytes to lipolytic agents such as epinephrine and glucagon. Fat cells of propylthiouracil-induced hypothyroid rats are unresponsive to lipolytic agents and the V-max of particulate low K-m cyclic AMP phosphodiesterase of these cells is elevated above normal. In vivo treatment of hypothyroid rats with triiodothyronine restores to control values both the lipolytic response of the fat cells to epinephrine and the V-max of the particulate bound low K-m cyclic AMP phosphodiesterase. No similar correlation is found with the soluble high K-m cyclic AMP phosphodiesterase. The phosphodiesterases of fat cells from normal and hypothyroid rats respond identically in vitro to propylthiouracil, triiodothyronine, methylisobutylxanthine, or theophylline, although the particulate low K-m cyclic AMP phosphodiesterase is inhibited to a greater extent than soluble cyclic guanosine 3':5'-monophosphate phosphodiesterase activity. Protein kinase of fat cells from hypothyroid rats can be stimulated by cyclic AMP to the same total activity as observed in fat cells of normal rats. However, less of the protein kinase in fat cells from hypothyroid rats was in the cyclic AMP-independent form. This shift in the equilibrium of protein kinase forms is consistent with an increased activity of low K-m cyclic AMP phosphodiesterase and probably results from a lowering of the lipolytically significant pool of cyclic AMP.

Adipose Tissue↗
PubMed1975

Cyclic nucleotide phosphodiesterases in uterine development.

Activities of cyclic nucleotide phosphodiesterase were studied in rat uterus as a function of age, DNA and protein content. Linear kinetics were observed for uterine homogenate cyclic GMP (cGMP) phosphodiesterase activity, but anomalous double-reciprocal plots, suggestive of multiple enzyme forms, were observed for cyclic AMP (cAMP) hydrolysis, cAMP phosphodiesterase was therefore measured at high and low substrate concentrations, 200 muM and 0.25 muM cAMP, respectively, to approximate multiple enzyme activities. Based upon total organ content, the total cAMP and cGMP phosphodiesterase activities increased throughout uterine development, from 5-50 days of age. On the same basis, the apparent low KM cAMP phosphodiesterase increased only between days 5 and 15 and showed no significant increase between days 15 and 50. On the other hand, specific activities of an apparent low KM cAMP phosphodiesterase, expressed per mg of protein or per mug of DNA, showed a marked reduction in activity between 30 and 50 days of age. Chronic administration of 17beta-estradiol to immature rats increased their uterine protein content and decreased the specific activity of the apparent low KM cAMP phosphodiesterase. In another estrogen target tissue, the anterior pituitary, protein and DNA content also increased during development but no changes in specific activities of cyclic nucleotide phosphodiesterase were noted. These results suggest the possible participation of cyclic nucleotide phosphodiesterases in the induction of uterine growth and development by ovarian hormones.

3',5'-Cyclic-AMP Phosphodiesterases↗