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Biomedical subjects

K G Morgan

Publications and source records attributed to K G Morgan.

119 records · Page 7Linked to original sources

Mechanisms of phasic and tonic actions of pentagastrin on canine gastric smooth muscle.

1. Pentagastrin increased the amplitude and frequency of spontaneous phasic contractions of gastric smooth muscle preparations from the antrum and corpus. Pentagastrin also increased the basal tone in the corpus but not in the antrum. 2. The increase in the amplitude of phasic contractions caused by pentagastri was associated with an increase in the amplitude and duration of the plateau of the action potential in both the antrum and corpus. 3. Voltage-tension curves generated by graded potassium depolariztion of the membrane potential defined a mechanical threshold for the muscle. 4. Comparison of the effects of pentagastrin to the voltage-tension curves indicated that the pentagastrin-induced depolarization of the resting potential was below threshold for the production of a contraction. In contrast, the movement of the top of the plateau potential to more depolarized potentials by this agent exactly followed the voltage-tension curve for the muscle, implying that both potassium and the plateau potential affected the same voltage-sensitive mechanism. 5. Pentagastrin caused an increase in conductance of antral preparations during the plateau of the action potential but not between action potentials. In corporal preparations, pentagastrin increased conductance during action potentials, but in addition increased conductance between action potentials. 6. The data indicate that pentagastrin increases the force of phasic contractions in antral and corporal smooth muscle by a voltage dependent process, probably involving the opening of voltage dependent calcium channels. In contrast, the data indicate that pentagastrin increases tone by a voltage independent process, possibly involving a nonregenerative increase in calcium movements through voltage independent channels.

Action Potentials↗

Intracellular electrical activity of canine and human gastric smooth muscle.

1. Intracellular recordings were obtained from circular smooth muscle fibres of the canine fundus, corpus, antrum and pylorus as well as from the human corpus and antrum. 2. In the canine stomach, all regions of the stomach except the fundus exhibited spontaneous action potentials. 3. The spontaneous action potential consisted of an upstroke potential and a plateau potential. 4. There were regional differences in the configuration of the plateau potential. Corporal and antral smooth muscle did not normally spike during the plateau potential whereas terminal antral and pyloric muscle usually showed spikes on top of the plateau potential. Near the intermediate sphincter, there was a zone of transition in which oscillations in potential of variable amplitude were superimposed on the plateau potential. 5. The configuration of the action potential of the human stomach was similar to the configuration of the canine action potential when the same region of the stomach was compared. 6. The ionic dependence of the plateau potential was studied in canine stomach in an area where neither oscillations nor spikes occurred. 7. In calcium-free solution, all spontaneous activity stopped. D600 selectively suppressed the size of the plateau potential. 8. Sodium-deficient solution reduced the size of the plateau potential. 9. These results suggest that both calcium and sodium may be involved as current carriers in the generation of the plateau potential.

Action Potentials↗

The inhibitory effects of vasoactive intestinal polypeptide on the mechanical and electrical activity of canine antral smooth muscle.

1. The inhibitory effects of vasoactive intestinal polypeptide (VIP) on the electrical and mechanical activity of canine antral smooth muscle were investigated. 2. In concentrations ranging from 5 X 10(-9) to 1 X 10(-7) M, VIP decreased the force of spontaneous contractions but had no measurable effect on spontaneous action potential complexes. 3. VIP had no effect on the increase in the amplitude and duration of the plateau potential and on the amplitude of contraction caused by a maximally effective concentration of acetylcholine. 4. VIP caused a significant decrease in the force of contraction caused by ED50 and threshold concentrations of acetylcholine. However, VIP had no measurable effect on the increase in the size of the action potential plateau caused by either concentration of acetylcholine. 5. VIP antagonized the increase in the amplitude of the plateau potential and the force of contraction induced by pentagastrin. It had no consistent effect on the pentagastrin-induced increase in frequency. 6. The data indicate that VIP acts as an inhibitor in this tissue in two distinct ways. It uncouples electromechanical coupling during spontaneous and acetylcholine-induced electrical and mechanical activity, and antagonizes pentagastrin-induced increases in electrical and mechanical activities.

Acetylcholine↗

Electrical and mechanical effects of molecular variants of CCK on antral smooth muscle.

Intracellular microelectrode and standard organ bath techniques were used to study in vitro the effects of three molecular forms of the peptide cholecystokinin on the electrical and mechanical activities of canine antral circular muscle. Three forms were studied: the carboxyl-terminal octapeptide of cholecystokinin (CCK-OP), the molecule containing 33 amino acid residues (CCK33), and the peptide termed "cholecystokinin variant" that contains 39 amino acids (CCK39). All three forms increased the force and frequency of spontaneous contractions. They also increased the frequency and the amplitude and duration of the plateau of the gastric action potential. Atropine did not block any of these effects, suggesting that the action of these peptides was largely due to a direct action on the smooth muscle. Complete dose-response curves were determined for the effect of these peptides on the force and frequency of contraction for muscle strips and for the effect on amplitude of the plateau and frequency of the action potential for single cells. CCK39 and CCK-OP had similar potencies and both forms were more potent than CCK33.

Action Potentials↗

Effects of pentagastrin, G17, and G34 on the electrical and mechanical activities of canine antral smooth muscle.

Intracellular microelectrode technique and standard organ bath technique were used to investigate the effects of pentagastrin, G17, and G34 on the electrical and mechanical activities of canine antral circular muscle. All three molecular forms increased the amplitude and duration of the plateau of the gastric action potential and the frequency of spontaneous action potentials. They also increased the amplitude and frequency of spontaneous contractions. G17 was equal to or less potent than pentagastrin in all of its actions on this tissue. G34 had an equal or greater activity than G17. The electrical studies indicate that G17 is active in this tissue in a physiological range of concentrations. The ED50 for the effect of G17 to increase the amplitude of the plateau potential is less than that for the effect of G17 on gastric secretion, indicating that this is a physiological action of gastrin. Atropine studies indicate that only part of the in vitro inotropic action of gastrin is caused by the release of acetylcholine from nerve terminals, but that the chronotropic action is attributable to a direct effect on the smooth muscle membrane.

Action Potentials↗

The mechanism of action of dantrolene sodium.

Dantrolene sodium is thought to affect some step in the excitation-contraction coupling process. Using a point voltage clamp to determine mechanical thresholds of individual fibers of frog, rat and goat skeletal muscle preparations, we found that dantrolene both raises (moves to more positive potentials) the rheobasic potential and increases the steepness of the strength-duration curve for mechanical threshold. The effect of raising the rheobase reaches a maximum at 1.2 x 10-5M dantrolene whereas the steepness effect occurs only at a saturating concentration (3.8x10-5M),indicating that dantrolene has two sites of action. The rheobase effect is absent below 18 degrees C (suggesting a phase transition) and it is competitively antagnoized by the calcium ionophore A23187 which can release calcium from the sarcoplasmic reticulum. The data indicate that dantrolene raises the rheobase by directly decreasing the release of calcium from the sarcoplasmic reticulum. We propose that dantrolene inhibits the movement of a natural calcium ionophore. Measurements of the voltage-dependent charge movement associated with excitation-contraction coupling showed that dantrolene did not significantly change the amount of charge moved. The time to peak of the ON current was not significantly changed, but that of the OFF current was significantly shortened. This action of dantrolene on the kinetics of the OFF current may account for its effect on the steepness of the strength-duration curve.

Animals↗

Myotonia and block of chloride conductance by iodide in avian muscle.

Immature chickens and adult pigeons whose drinking water contained 3% KI for 1--10 days developed myotonia, characterized by stiffness on sudden movement and abnormal repetitive firing of skeletal muscle fibers. Component resting membrane conductances, excitability, and membrane potentials of biventer cervicis muscle fibers from adult pigeons were measured in vitro at 38--39degreesC. Fibers from iodide-treated pigeons in normal solution and fibers from untreated pigeons in I--containing solution (15--120 mM) responded repetitively to electrical and mechanical stimulation. Resting anion conductance (Ganion), assumed to be the sum of C1- and I- conductances, of fibers from iodide-treated pigeons decreased nonlinearly from 2,565 to 266 mumho/cm2 when the bath concentration of I- was increased from 0 to 120 mM. Potassium conductance was assumed constant at 577 mumho/cm2. Ganion of fibers from iodide-treated pigeons was 50% of control and equaled that of untreated fibers in 15 mM I- containing medium. Reduction of the stabilizing Ganion and increased mechanical responsiveness can account for the iodide-induced myotonia in birds.

Animals↗

Primary small cell neuroendocrine carcinoma of the kidney.

The histological, immunohistochemical, and ultrastructural features of a primary small cell neuroendocrine carcinoma of the renal parenchyma are described. Tumor cells were positive for cytokeratin, neuron-specific enolase, and Leu 7, but Grimelius- and chromogranin-negative. They also exhibited positivity with anti-MIC2 antibody. By electron microscopy, tonofibrils, primitive desmosomes, and dense-core granules with a neuroendocrine appearance were present. This is only the 7th recorded example of such a tumor at this site, which showed an aggressive course characterized by widespread bony metastases.

Adult↗