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Biomedical subjects

W J Thompson

Publications and source records attributed to W J Thompson.

At least 145 records · Page 8Linked to original sources
PubMed1979

Neural control of heartbeat in the leech and in some other invertebrates.

The heartbeat of the leech Hirudo consists of the contractile rhythm of the circular muscles in the wall of a bilateral pair of celomic sinuses, the heart tubes, that run the length of the leech body. The constriction cycles of the segmental heart-tube sections are coordinated so that on one body side they constrict in a rear-to-front progression (peristalsis), while on the other side they constrict nearly in concert (nonperistalsis). Spontaneous right-left reciprocal transitions between peristaltic and nonperistaltic coordination modes occur every few dozen heartbeat cycles. The constriction of each segmental heart-tube section is controlled via excitatory synapses by a rhythmically active heart motor neuron, or HE cell, of which 17 bilateral pairs are iterated in segmental ganglia of the ventral nerve cord. The activity rhythm of the HE cell ensemble is in turn controlled via inhibitory synapses by a rhythmically active heart interneuron, the HN cell, of which seven bilateral pairs are iterated in the rostral segmental ganglia. The HN heart interneuron owes its activity rhythm to an endogenous polarization cycle, and the cycles of all members of the HN cell ensemble are locked into an appropriate phase relation thanks to their mutual interconnection via excitatory and inhibitory synaptic connections. The observed activity pattern and identified synaptic connections of HE cells and HN cells can account not only for the generation of the two bilaterally asymmetric heartbeat coordination modes but also for the right-left coordination mode transitions. In contrast to the heartbeat of Hirudo, the beat of the single-chambered heart of the lobsters Panulirus and Homarus is controlled by a set of nine rhythmically active neurons that make up the cardiac ganglion. Of these, five larger cells are heart motor neurons that innervate the heart muscle fibers via excitatory synapses. The remaining four smaller neurons of the cardiac ganglion are interneurons that provide excitatory input to each other and to the heart motor neurons. Although all the neurons of the cardiac ganglion appear capable of producing their own endogenous polarization rhythm, it is currently believed that one of the interneurons acts as a pacemaker for the whole ensemble of interneurons and motor neurons. The beat of the two-chambered heart of the marine snail Aplysia is generated by yet an entirely different mechanism. Here, the basic contractile rhythm of the heart is due to an endogenous polarization cycle of the heart muscle fibers. That myogenic rhythm is controlled and modulated by a set of cardiovascular motor neurons located in the abdominal ganglion, some of which make excitatory and others of which make inhibitory connections with the heart muscle fibers. The activity of these cardiovascular motor neurons is controlled by three types of heart interneurons via both inhibitory and excitatory connections. The interneurons are in turn interconnected in a manner that prevents the simultaneous activation of antagonistic cardiac motor acts...

Action Potentials↗
PubMed1978

Activation of mammalian cyclic AMP phosphodiesterases by trypsin.

BHK fibroblasts contain two forms of cyclic AMP phosphodiesterase 3':5'-cyclic nucleotide 5'-nucleotidohydrolase EC 3.1.4.17) as analyzed by linear sucrose gradient fractionation; a 3.6-S form (peak I) and a 6.7-S form (peak II). Peak I is specific for cyclic AMP as substrate and displays Michaelis-Menten kinetics with an apparent Km of 2--3 micrometer. Peak II hydrolyzes cyclic GMP and displays anomalous kinetics for cyclic AMP hydrolysis. The activity of isolated peak II for cyclic AMP is increased by storage at 4 degrees C, treatment with trypsin, or treatment with rat brain and BHK fibroblast activator proteins. The activity of isolated peak I is unaffected by these conditions. Linear sucrose gradient fractionation demonstrates that activation of peak II by trypsin leads to the formation of a 3.6-S cyclic AMP-specific enzyme form, possibly peak I. In contrast to BHK fibroblasts (and most other mammalian tissues), rat uterus contains only one form of cyclic nucleotide phosphodiesterase on linear sucrose gradients, a 7-S form capable of hydrolyzing both cyclic AMP and cyclic GMP. Treatment of rat uterine supernatant with trypsin leads to the appearance of a 4-S, cyclic AMP-specific form with properties similar to that of BHK peak I. These data suggest that the kinetically complex, higher molecular weight cyclic nucleotide phosphodiesterases may consist of more than one catalytically active site and that multiple forms of the enzyme arise through dissociative mechanisms, possibly as a means of in vivo regulation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1978

Characterization of soluble uterine cyclic nucleotide phosphodiesterase.

Soluble cyclic nucleotide phosphodiesterase of rat uterus displays distinct structural and regulatory properties. Like phosphodiesterases from many mammalian sources the soluble uterine enzyme system exhibits nonlinear Lineweaver--Burk kinetics with cyclic adenosine 3':5'-monophosphate (cAMP) as substrate (apparent Kms congruent to 3 and 20 micron) and linear kinetics with cyclic guanosine 3':5'-monophosphate (cGMP) as substrate (apparent Km congruent to 3 micron). Unlike most other mammalian phosphodiesterases, however, numerous separation procedures reveal only a single form of uterine phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP. A single form of the enzyme is observed upon sucrose gradient centrifugation (7.9 S), agarose gel filtration, and DEAE-cellulose chromatography at either pH 8.0 OR 6.0. Heat denaturation (50 degrees C) of soluble uterine phosphodiesterase causes the loss of both cAMP and cGMP hydrolytic activities at the same rate. Isoelectric focusing reveals major (pI = 5.2) and minor forms (pI = 5.8) of phosphodiesterase which both catalyze the hydrolysis of the two cyclic nucleotide substrates. In vivo administration of estradiol produces identical decreases in the activities of cAMP and cGMP phosphodiesterase. These results raise the possibility that the uterus contains a single form of soluble phosphodiesterase which catalyzes the hydrolysis of both cAMP and cGMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

Cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) in lymphocytes from patients with stage III and IV squamous cell carcinoma of the head and neck.

In vivo skin tests using multiple recall and primary antigens such as dinitrochlorobenzine (DNCB) have established that there is decreased cellular-mediated immune response in patients with squamous cell carcinomas of the head and neck. In vitro testing of lymphocytes using blastogenic mitogens as a measure of lymphocyte function has not always shown a statistical difference between patients and controls.cAMP-PDE was assayed in lymphocytes from normal controls-patients with benign conditions in various age groups. No significant difference was found in the specific activity (Vmax) or affinity (Km) in these groups. The mean average was used as a normal control value. In lymphocytes from untreated patients with Stage III and IV squamous cell carcinomas of the head and neck, the Vmax and Km of cAMP-PDE were higher than the controls. This difference was statistically significant. Postoperative values were also determined byt were not statistically different. There were no differences found in blastogenesis in these two groups.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1977

Rat gastric mucosal adenylyl cyclase.

Prostaglandin E1, epinephrine, secretin, and glucagon are known inhibitors of gastric acid secretion, and each agent stimulated mucosal membrane (600 X g pellet) adenylyl cyclase activity from the corpus of the rat stomach. This adenylyl cyclase activity was also stimulated by 5'-guanylyl-imidodiphosphate and sodium fluoride but not by guanosine-5'-triphosphate. By contrast, the gastric acid secretagogues, pentagastrin, histamine, and carbachol, had no effect on basal or prostaglandin E1-stimulated mucosal adenylyl cyclase activity. Most of the sodium fluoride- and hormone-stimulated adenylyl cyclase of the corpus mucosa was contained in the 600 X g membrane fraction. The enzyme exhibited Michaelis-Menten kinetics with respect to the concentration of ATP, with an apparent Km of 0.25 mM. Histamine did not stimulate rat mucosal adenylyl cyclase activity under a variety of conditions, but did stimulate the same enzyme in guinea pig gastric fundic mucosa, an enzyme also activated by prostaglandin E1. These studies do not support the hypothesis that cyclic AMP mediates the actions of gastric acid secretagogues on the parietal cell in the rat.

Adenylyl Cyclases↗
PubMed1977

Activation of rat gastric mucosal adenylyl cyclase by secretory inhibitors.

Prostaglandin (PG) E1, E2, A1, and A2 stimulated rat gastric corpus mucosal membrane adenylyl cyclase activity. PGE1 (Kalpha congruent to 8 muM) affected the maximum velocity but not the affinity of the enzyme for ATP and maximum PGE1 activation was not affected by histamine H1 or H2 receptor antagonists. 5'-Guanylyl-diphosphoimide (Gpp(NH)p), but not GTP, stimulated both the basal and PGE1-stimulated adenylyl cyclase activities, although the percentage stimulation by maximal PGE was the same with or without Gpp(NH)p. NaF stimulation was also additive to that of PGE1. Secretin also stimulated gastric mucosal adenylyl cyclase activity (Kalpha congruent to 30 nM). Maximal secretin activation was not additive to that of PGE1, suggesting a coupling to the same adenylyl cyclase catalytic site. These studies suggest that mucosal membranes may contain beta-adrenergic receptors. The adenylyl cyclase activating agents used in this study, PGE1, secretin, and the catecholamines, are all known inhibitors of gastric acid secretion, suggesting a possible involvement of cyclic AMP in the inhibition of acid secretion in the rat stomach.

Adenosine Triphosphate↗
PubMed1977

Sonication as a tool for the study of adenylyl cyclase activity.

The technique of sonication was applied in studying adenylyl cyclase activity of cultured fibroblasts. Exposure of BHK 21 c/13 to brief periods of low power sonication gives cell preparations with greater basal, fluoride and hormone sensitive adenylyl cyclase activites than those of broken cell preparations of homogenized cells. The sonicated cells provide a convenient method to study adenylyl cyclase since they are added directly to the adenylyl cyclase reaction vessels without further processing. Maximal epinephrine stimulated activity in sonicated cells is nearly equivalent to that activated by sodium fluoride, but the apparent affinity of the enzyme system is similar to that of broken cell preparations. Furthermore, broken cell preparations of sonicated cells possess greater adenylyl cyclase activity than broken cell preparations of unsonicated cells. This procedure may provide a useful tool for the analysis of the hormonal regulation of adenylyl cyclase activity of isolated cells.

Adenylyl Cyclases↗
PubMed1976

Cyclic adenosine 3':5'-monophosphate phosphodiesterase. Distinct forms in human lymphocytes and monocytes.

Adenosine 3':5'-monophosphate (cyclic AMP) phosphodiesterase activity of normal human peripheral blood leukocyte suspensions containing 90% lymphocytes and 10% monocytes showed anomalous kinetic behavior indicative of multiple enzyme forms. Kinetic analyses of purified lymphocyte (99%) or monocyte preparations (95%) indicated that only one type of phosphodiesterase was present in each cell type. None of the preparations contained any detectable guanosine 3':5'-monophosphate (cyclic GMP) hydrolytic activity. The lymphocyte enzyme had an apparent Km congruent to 0.4 muM for cyclic AMP and Vmax congruent to 0.5 picomoles/min/10(6) cells. These kinetic parameters were confirmed by several cell purification techniques used alone and sequentially. Sedimentation velocity analyses indicated that the higher Km monocyte enzyme had a molecular weight near 45,000 and that the lower Km lymphocyte enzyme most likely had a molecular weight near 98,000. A variety of procedures led to a loss of the higher molecular weight, high affinity enzyme leaving only the enzyme of 45,000 daltons with a much lower substrate affinity. A long term, stable human lymphoblastoid cell line had cyclic AMP phosphodiesterase activity that was similar to the lymphocyte enzyme by both physical and kinetic criteria. Lymphocyte cyclic AMP phosphodiesterase appears to be a soluble enzyme whose pH and temperature optima and cationic requirements are similar to those of other mammalian phosphodiesterases. The distinct cyclic AMP phosphodiesterase forms of these cells may possibly represent the basic, active subunit of mammalian cyclic nucleotide phosphodiesterases. We hypothesize that the extremely high affinity cyclic AMP phosphodiesterase of normal lymphocytes plays an important role in the regulation of normal function in these cells, and also in the rapid proliferative responses characteristic of the stimulated lymphocyte.

3',5'-Cyclic-AMP Phosphodiesterases↗