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Biomedical subjects

K M Sanders

Publications and source records attributed to K M Sanders.

At least 253 records · Page 14Linked to original sources
PubMed1985

Origin and spread of slow waves in canine gastric antral circular muscle.

Electrical slow waves recorded from circular muscle cells near the myenteric and submucosal plexuses were found to be significantly different. By measuring the latencies between the arrival of evoked events at two recording sites, slow wave conduction velocities were determined in the three dimensions of circular muscle. Slow waves propagated more rapidly in the axis parallel to the circular fibers than in the axes perpendicular to the circular fibers. The rates of slow wave propagation were also determined in axes parallel and perpendicular to fibers in myenteric and submucosal circular muscles. Slow waves conducted more slowly in the circular muscle near the submucosa than in circular muscle near the myenteric plexus. From conduction velocity measurements, a technique was developed to determine the pacemaker site of spontaneous slow waves in a muscle strip. These data demonstrate that slow waves originate from multiple discrete foci; in muscle strips cut along the long axis of the stomach, these foci are found predominantly in the orad region of the muscle strip; and slow waves originate in the outer myenteric half of the muscle.

Action Potentials↗
PubMed1985

Effects of ethyl alcohol on phasic and tonic contractions of the proximal stomach.

The effects of ethyl alcohol (EtOH) on the contractile activities of canine gastric corpus and fundus circular muscles were studied. EtOH, 0.1 to 1%, inhibited phasic contractions of corpus muscles but enhanced tonic contractions. These effects were both concentration dependent. The same range of EtOH concentrations caused a transient rise followed by a fall in the level of tone of fundic muscles. The effects of EtOH on ACh-stimulated contractions were also studied. Phasic contractions were stimulated by ACh and inhibited by EtOH. EtOH augmented the tone responses of both corpus and fundus muscles to ACh. Experiments were also performed to test whether EtOH had specific and direct effects on these muscles. The effects of EtOH were apparently not mediated by prostaglandins or Ach and were not, at least in corpus muscles, a nonspecific result of the hyperosmolarity of EtOH solutions. The data supplement previous studies on muscles of the distal stomach where the effects of EtOH were inhibitory to phasic contractions. The finding that the proximal stomach responds to EtOH with tonic contraction may help explain some of the controversy in the literature about the effects of EtOH on gastric emptying.

Acetylcholine↗
PubMed1984

Evidence that prostaglandins are local regulatory agents in canine ileal circular muscle.

Studies were performed to determine the role of endogenous prostaglandins (PG) in regulating mechanical and electrical activities of canine ileal circular muscles. Indomethacin, a prostaglandin synthesis blocker, enhanced the amplitude of spontaneous and acetylcholine-stimulated contractions. The increase in mechanical activity caused by indomethacin was accompanied by decreased release of 6-keto-PGF1 alpha, the spontaneous metabolite of prostacyclin, from the muscle. The electrical mechanisms responsible for the changes in mechanical activity caused by indomethacin were investigated by intracellular measurement of electrical activity. The enhanced contractions due to indomethacin correlated with enhanced electrical slow-wave amplitude and generation of action potentials. After indomethacin treatment muscles were exposed to several exogenous prostaglandins to determine which of these compounds might reverse the mechanical effects of indomethacin. Prostacyclin reversed the effects of indomethacin, and PGE2 reversed some of the effects of indomethacin. Prostacyclin also decreased the amplitude of electrical slow waves and abolished action potentials. These electrical effects were associated with decreased contractile amplitude. It is concluded that the dominant prostaglandin responsible for the "prostaglandin effect" in canine ileal circular muscle must be inhibitory to spontaneous and acetylcholine-stimulated contractions. The mechanical effects attributed to endogenous prostaglandin appear to be due to an electrical mechanism. Based on the evidence presented prostacyclin emerges as the most likely candidate for the role of "dominant" prostaglandin, but PGE2 may also contribute as a modulator of electrical and mechanical activities.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Role of prostaglandins in regulating gastric motility.

Muscles of the stomach possess the ability to synthesize several prostaglandins. These compounds function as local regulatory agents by influencing the motor performance of the muscle cells. In the distal stomach the dominant effect of endogenous prostaglandins is to decrease the amplitude of contractions and decrease the ability of the muscles to respond to excitatory stimuli. Prostaglandins also have a chronotropic role in the distal stomach, and they are responsible for the frequency effect of gastrin pentapeptide. In the proximal stomach prostaglandins have an opposite role; they promote tonic contraction. Because of the diverse effects of prostaglandins, they probably have complicated effects on gastric motility. In general, emptying of solids should be retarded by endogenous prostaglandins, whereas emptying of fluids may be facilitated by these compounds. Overproduction of prostaglandins may produce abnormal motility patterns and affect gastric emptying. A case of gastric pseudoobstruction apparently involving prostaglandins is discussed.

Animals↗
PubMed1984

A technique to locate the pacemaker in smooth muscles.

A technique was developed to locate the site of slow-wave origin (pacemaker) in a sheet of smooth muscle tissue. Evoked slow waves were used to measure conduction velocities in the two dimensions of sheets of smooth muscle. These conduction velocities were used to "triangulate" to the pacemaker site by an iterative minimization process. The model was tested by triangulating to events evoked from known regions within sheets of canine gastric muscle. The technique was used to determine the sites of origin of spontaneous slow waves and the shift in the spontaneous pacemaker caused by localized injury. This technique will be useful in locating pacemaker regions and to study the factors that affect the origin and frequency of slow waves in syncytial tissues. The triangulation technique should be applicable to intact organs as well as isolated sheets of muscle.

Animals↗
PubMed1983

Electroimmunoassay. A new competitive protein-binding assay using antibody-sensitive electrodes.

A novel technique is reported in which an antibody-sensitive electrode for anti-prostaglandin E2 antisera was used to measure solution-phase PGE2 in nanomolar quantities. The electrode was constructed by incorporating a cation-selective ionophore-hapten (PGE2) conjugate into a polyvinyl chloride membrane. Transmembrane potential in a fixed potassium gradient was measured. The addition of anti-PGE2 antisera changed membrane potential in a concentration-dependent manner. The effect of anti-PGE2 antibodies on membrane potential was decreased by adding free PGE2 to the buffer-containing antisera. With this technique a competitive protein-binding assay was developed, and standard curves for solution-phase PGE2 were generated over a concentration range of 1 to 1,000 nM. The assay was relatively specific for PGE2; PGD2 and PGF2a had only minor effects on transmembrane potential over the effective concentration range for PGE2.

Animals↗
PubMed1983

Excitation-contraction coupling without Ca2+ action potentials in small intestine.

Sensitive mechanical and intracellular electrical recordings showed that phasic contractions occurred in response to electrical slow waves in the absence of Ca2+ action potentials. Drugs that either enhanced or depressed slow waves were used to study the relationship between slow-wave amplitude and the amplitude of the phasic contractions. Acetylcholine (Ach) (10(-8) to 3 X 10(-7) M) increased slow waves and contractions without causing action potentials. When ACh was raised to 10(-6) M, action potentials were elicited and accompanying contractions increased in amplitude by at least a factor of five. The Ca2+ channel blocker, Mn2+ (0.5 mM), decreased slow-wave amplitude and the associated phasic contractions. These data agree with a previous study (12), suggesting that an oscillation in intracellular Ca2+ occurs during each slow-wave cycle. The present study suggests that the increase in intracellular Ca2+ during the slow wave is sufficient to activate the contractile apparatus.

Acetylcholine↗
PubMed1983

Prostaglandin synthesis by microsomes of circular and longitudinal gastrointestinal muscles.

Experiments were performed to determine whether longitudinal and circular muscles from various regions of stomach and small bowel had the capacity to convert arachidonic acid (AA) to prostaglandins (PGs). PG production by the microsomal fractions of isolated muscles was assayed by determining the conversion of [14C]AA to 14C-labeled 6-keto-PGF1 alpha, PGF2 alpha, PGE2, PGD2, PGA2, and thromboxane B2. Individual PGs were identified by thin-layer chromatography. The metabolism of [14C]AA to [14C]PGs was linearly related to substrate concentration, enzyme concentration, and incubation time at 37 degrees C and was inhibited in a dose-dependent manner by indomethacin. Longitudinal and circular muscles from all tested regions (corpus, fundus, antrum, pylorus, duodenum, jejunum, and ileum) synthesized PGs. In all regions the major end products of AA metabolism were 6-keto-PGF1 alpha, PGE2, and PGF2 alpha. The data indicate that circular and longitudinal muscles from all regions of the stomach and small bowel contain the enzymatic apparatus necessary to convert AA into prostaglandins.

Animals↗
PubMed1982

Ethyl alcohol interferes with excitation-contraction mechanisms of canine antral muscle.

Ethyl alcohol (EtOH) inhibited spontaneous and acetylcholine (ACh)-induced contractions in a dose-dependent manner (0.1-2.5%). These concentrations also reduce the amplitudes of intracellularly recorded slow waves. The effects of EtOH do not appear to be mediated by adrenergic or prostaglandin mechanisms, nor can they be explained on the basis of hyperosmolarity. At higher concentrations (1-10%), EtOH totally abolished phasic contractile activity and caused tonic contraction. ACh was not able to restore normal phasic contractions to muscles treated with EtOH above 2.5% and, in fact, further enhanced the force of the tonic contraction. The membrane potential response to EtOH above 1% was biphasic; the membrane transiently hyperpolarized and then tonically depolarized. It appears that many of the effects of EtOH on gastric emptying might be due to direct interference by EtOH in the membrane events leading to excitation-contraction coupling in gastric smooth muscle.

Acetylcholine↗
PubMed1982

Effect of neurotensin on mechanical and intracellular electrical activity of the canine stomach.

Intracellular microelectrode and standard organ bath techniques were used to study in vitro the effects of neurotensin on the electrical and mechanical activities of canine antral circular smooth muscle. Neurotensin reduced or abolished spontaneous contractions. Muscarinic and adrenergic antagonists and tetrodotoxin did not block the effects of neurotensin, suggesting that the action of neurotensin was due to a direct action on the smooth muscle cell. Although the inhibitory effect of norepinephrine and neurotensin was similar, the effect of neurotensin did not appear to occur by an adrenergic mechanism because alpha- and beta-receptor blockade had no effect. Neurotensin also reduced or abolished contractions stimulated by pentagastrin and acetylcholine. The inhibitory effect of neurotensin on spontaneous acetylcholine- and pentagastrin-stimulated contractions was associated with a decrease in the amplitude and duration of the plateau potential of the gastric action potential. The data suggest that modulation of antral contractions by neurotensin occurs through a voltage-dependent mechanism that operates during the plateau potential.

Acetylcholine↗
PubMed1981

Does endogenous prostaglandin affect gastric antral motility?

Intracellular electrical activity and muscle contraction were recorded simultaneously from circular muscle of the canine antrum. Treatment with indomethacin enhanced the plateau phase of the spontaneously occurring gastric action potential and the amplitude of the phasic contraction. Exogenous PGE2 reversed this effect of indomethacin. Treatment with indomethacin also enhanced the electrical and mechanical responses to pentagastrin; this enhancement was also reversed by PGE2. Considered together, these results suggest that endogenous prostaglandin, probably of the E series, tonically suppresses the spontaneous electrical and mechanical activities of antral circular muscle and the responsiveness of the muscle to excitatory stimuli.

Animals↗
PubMed1978

Effects of endogenous prostaglandin E on intestinal motility.

The role of endogenous prostaglandin E (PGE) in the regulation of intestinal motility in situ was studied in cats anesthetized with pentobarbital. The basal concentration of PGE in the ileum was found by radioimmunoassay to be 3.3 +/- 0.6 ng PGE per g wet wt (chi +/- SE, n = 12). Intramesenteric arterial infusion of acetylcholine (ACh) (100 microgram/min) increased intestinal motility, and PGE concentration rose to 6.7 +/- 0.8 ng/g. Intravenous infusion of indomethacin (4 mg/kg) enhanced spontaneous and ACh-induced motility and abolished the ACh-induced rise in ileal PGE concentration. We conclude that basal PGE synthesis limits the motility of the resting and ACh-stimulated cat ileum.

Acetylcholine↗
PubMed1978

Endogenous prostaglandin E and contractile activity of isolated ileal smooth muscle.

The effects of endogenous prostaglandin E (PGE) on the contractile activity of isolated cat ileal muscle rings were studied. Force development in circularly oriented muscle fibers were recorded. The muscles contained a mean basal PGE concentration of 1 +/- 0.6 ng PGE per g wet wt (mean +/- SE) as measured by radioimmunoassay. Acetylcholine (ACh) or elevated potassium caused contractions and enhanced PGE concentration (P less than 0.05). Removing Ca2+ from high potassium solutions blocked contraction, but PGE concentration still increased (P less than 0.02). The prostaglandin synthetase inhibitors, indomethacin and 5,8,11,14-eicosatetraenoic acid (ETA) reduced PGE concentration in muscles (less than 50 pg PGE per g muscle) and increased the magnitude of contractions induced by either ACh or elevated potassium. Spontaneous contractions were observed in many tissues after inhibition of PGE synthesis. In conclusion, endogenous PGE limits spontaneous and depolarization-induced muscular activity in cat ileal circular muscle. Synthesis of PGE was increased by depolarizing stimuli whether or not contractions were blocked by the removal of external calcium.

Acetylcholine↗
PubMed1975

Inhibition of in vivo Neural Vasoconstriction by exogenous catecholamines.

Intaarterial infusions of norepinephrine and dopamine markedly attenuated the mesenteric vasoconstrictor response to periarterial nerve stimulation in anesthetized cats, but did not attenuate the response to intravenous norepinephrine. The degree of attenuation was independent of stimulation voltage, but inversely related to frequency. The results are compatible with previous in vitro evidence that NE and DA decrease adrenergic transmitter release during nerve stimulation.

Animals↗