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R F Coburn

Publications and source records attributed to R F Coburn.

At least 55 records · Page 3Linked to original sources
PubMed1981

Oxygen-induced contraction in the guinea pig neonatal ductus arteriosus.

We investigated the mechanism of oxygen-induced contractions in ductus arteriosus isolated from neonatal guinea pig. A preparation equilibrated at low Po2 (less than 40 mm Hg) displayed a steady membrane potential of -54.8 mV. Application of oxygen (Po2 (less than approximately or equal to 300 mm Hg) resulted in: (1) stepwise development of tension coupled to action potentials and (2) sustained membrane depolarization to -32.9 mV associated with tonic contraction. Mechanical sensitivity to oxygen persisted at any[K]o up to 126 mM, and tension was always larger at a given [K]o or a given membrane potential with high Po2 than with low Po2. The change in membrane potential per decade change in [K]o was 35 mV at low Po2 and 16 mV at high Po2. Oxygen contractions occurred when the ductal strips were bathed in K-free media or exposed to ouabain. We conclude that oxygen caused a conductance change in the sarcolemma resulting in depolarization, which is coupled to contraction. There is also evidence of a membrane potential-independent contraction mechanism.

Animals↗
PubMed1980

Calcium dependence of prostaglandin release from the guinea pig Taenia coli.

We studied the calcium dependency of the stimulation of prostaglandin synthesis which occurs when perfusing strips of guinea pig Taenia coli with potassium-free media. Stimulation was rapidly reversed by removal of extracellular Ca from the bathing solution. The Ca ionophore A23187 markedly stimulated prostaglandin E2 synthesis, an effect that is dependent on the presence of extracellular Ca. Prostaglandin E2 production in strips in potassium-deficient media was also sensitive to increases in extracellular Ca, and was augmented at concentrations of 7-15 mM. In strips which had been incubated with [3H]arachidonic acid, exposure to potassium-free media caused an increased release of [3H]arachidonic acid and [3H]prostaglandin E2. Release of these labeled compounds with the strips in potassium-free media was further augmented by increasing extracellular [Ca2+] from 2.5 to 10 mM. Treatment with the Ca antagonist agent verapamil did not influence activation of prostaglandin synthesis by potassium-deficient media. The presence of Mn2+ of Ba2+ had similar effects on prostaglandin synthesis, although they had opposite effects on mechanical activity. We conclude that a plasma membrane associated Ca pool is involved in activation of phospholipid metabolism which results in release of esterified arachidonic acid and subsequent prostaglandin synthesis. This Ca pool is in rapid equilibrium with extracellular Ca, is not influenced by cytoplasmic Ca, and is not related to Ca involved in Ca gating in the surface membrane. These data also indicate dissociation between processes involved in muscle contraction and activation of prostaglandin synthesis.

Animals↗
PubMed1980

Evidence for oscillation of prostaglandin release from spontaneously contracting guinea pig taenia coli.

Two strips of guinea pig taenia coli were mounted 1-2 mm apart in a small organ bath. One of the strips was incubated before mounting with indomethacin, which inhibited release of prostaglandin E2 for at least 4 h to levels not detectable by biological assay. Both stretch-evoked contractions or spontaneous contractions of the prostaglandin-releasing strip reduced the contraction time intervals between spontaneous contractions in the paired strip. Neither stretch-evoked nor spontaneous contractions of the nonprostaglandin-releasing strip influenced spontaneous contractions in the paired strip. With the strips widely separated, stretch-evoked contractions of the prostaglandin-releasing strips caused shortened contraction-time intervals in the paired strips, but spontaneous contractions had no such effect. Rat fundus, separated 1-2 mm from prostaglandin-releasing taenia coli, showed small contractions occurring at the same frequency as spontaneous taenia contractions. These rat fundus contractions were abolished by indomethacin. Data show that there is communication between the prostaglandin-releasing strip and the nonprogestaglandin-releasing strip, There is evidence that this communication was mediated by released prostaglandin E2 and that release of this mediated is augmented during spontaneous contractions of guinea pig taenia coli.

Animals↗
PubMed1979

Zero extracellular K+ and prostaglandin E release in the guinea-pig taenia coli.

Prostaglandin E release rates from isolated strips of guinea-pig taenia coli increased during exposure to zero K+ bathing fluid, from control values of 0.78 +/- 0.11 ng/g per min to levels as high as 29.2 ng/per min. Release rates increased for 40-50 min and then remained constant or fell despite progressive increases in intracellular sodium [Nai+] or fall in intracellular potassium [Ki+]. Readmittance of K+ to the bathing solution resulted in rapid reversal of elevated prostaglandin E release rates. [Nai+] and [Ki+] were markedly more abnormal in strips exposed to zero K+ for 70-201 min compared to 30-min exposures. Upon the readdition of K+ after long zero K+ exposure, the rate of prostaglandin E release fell long before [Nai+] and [Ki+] returned to control levels. After K+ was readded to the bathing solution, the ion concentration of tissues exposed to zero K+ for 30 min returned to normal much more quickly than did those of tissues exposed for the longer time periods, yet the exponential rate constants for fall of prostaglandin E release rate after K+ was added were not significantly different after short or long zero K+ exposure. Thus there was a dissociation between the return of [Nai+] and [Ki+] and the fall of prostaglandin E release rate to control levels. Ouabain augmented prostaglandin E release under conditions where [Ki+] could not fall. Addition of known neurotransmitters present in this tissue to the bathing fluid did not augment prostaglandin E release. Guinea-pig taenia coli strips that had been incubated with [3H]arachidonic acid, constantly released [3H]arachidonic acid and [3H]prostaglandin E and a prostaglandin which cochromatographed with prostaglandin E but could not be converted to prostaglandin B by alkali and was shown to be 6-ketoprostaglandin F1 alpha. Release of [3H]arachidonic acid and [3H]prostaglandin E plus 6-[3H]ketoprostaglandin F1 alpha was increased when strips were exposed to zero K+. Data obtained in this study suggest the augmented prostaglandin E release seen during zero K+ or ouabain is related to increased availability of unbound arachidonic acid at the site of cyclooxygenase in the cell. Augmented prostaglandin E release is apparently not related to alterations in intracellular electrolyte concentrations or release of known neurotransmitters.

Acetylcholine↗
PubMed1978

Effect of O2 exposure on pulmonary metabolism of prostaglandin E2.

The effect of exposure to oxygen on lung metabolism of prostaglandin E2 to 15-keto-prostaglandin E2 and 13-14-dihydro-15-keto-prostaglandin E2 was studied in the isolated, perfused rat lung. During a 30-sec period, lungs were infused with varying concentrations of prostaglandin E2 labeled with hydrogen-3 and the fraction metabolized during one passage was determined. At a prostaglandin E2 concentration of 5 nM, which approximates that in normal mixed venous blood, an average of 93 per cent of infused prostaglandin was metabolized by normal lungs. At prostaglandin E2 concentrations of 2 to 70 micrometer, the fraction metabolized decreased. The computed concentration of prostaglandin E2 for half-maximal rate of metabolism was 4.2 micrometer. Metabolism of prostaglandin E2 by isolated lungs was unaffected by exposure of rats to greater than 97 per cent oxygen at 1 atmosphere absolute for 24 hours, but was markedly depressed after both 36 and 48 hours of hyperoxia. These results indicate that exposure of the rat to oxygen for 36 and 48 hours is associated with decreased ability of the lung to metabolize prostaglandin E2 to its keto derivatives and may result in increased concentration of prostaglandin E2 in the systemic arterial blood.

Animals↗
PubMed1977

Na+-K+-ATPase inhibition stimulates PGE release in guinea pig taenia coli.

Inhibition of the plasma membrane enzyme Na+-K+-ATPase by ouabain zero extracellular K+, or low extracellular Na+, markedly augmented prostaglandin E release from the guinea pig taenia coli. Data suggest this phenomenon may be linked directly to Na+-K+-ATPase or Na+ pump activities, or changes in intracellular K+ concentration. The augmented prostaglandin E release was not due to changes in intracellular Na+, Ca2+, pH, or membrane potential, resulting from Na+ pump inhibition. The characteristics of the plasma membrane may exert a control on prostaglandin E release in this smooth muscle.

Adenosine Triphosphatases↗
PubMed1977

Membrane potential-dependent and-independent tension in the canine tracheal muscle.

We used the double sucrose gap apparatus to describe properties of electromechanical coupling in canine trachealis muscle, during infusion of elevated K+ and 5-hydroxytryptamine (5-HT). With 59 mM K+ and 5-HT, quasi-steady-state relationships of membrane depolarization and tension indicate electromechanical coupling, but for a given increase in tension much smaller membrane depolarizations were seen with 5-HT than with 59 mM K+. Evoked displacements of the membrane potential with anodal or cathodal current caused relaxations or contractions, respectively, and graded displacements resulted in graded tension changes. Reversal of 59 mM K+ membrane depolarization with long anodal current pulses resulted in nearly complete reversal of K+ tension, but reversal of 5-HT membrane depolarization caused tension reversal of only 20 to 40%. Data partially define electromechanical coupling in canine trachealis muscle provide evidence for membrane potential-independent tension with 5-HT at concentrations giving near threshold to maximal 5-HT tension.

Animals↗
PubMed1976

Endogenous prostaglandin in guinea pig taenia coli.

Prostaglandin (PGE) is synthesized in the guinea pig taenia coli. A low threshold concentration for an effect of exogenous PGE1 or PGE2 on spontaneous mechanical activity was demonstrated. The PG synthetase inhibitors aspirin, indomethacin, and 5,8,11,14-eicosatetraynoic acid, at concentrations that inhibited PGE efflux, had effects on spontaneous mechanical activity, membrane potential, membrane resistance, and evoked and spontaneous action potentials (single and double sucrose-gap methods) that were consistent with an action due to inhibition of membrane PGE concentration. The threshold concentration of indomethacin, which inhibited PGE efflux, was the same as the concentration that inhibited spontaneous mechanical activity. Pretreatment with ouabain (10(-6)-10(-5) g/ml) or elevated extracellular K+ (29 and 126 mM) made the guinea pig taenia coli entirely refractory to exogenous PGE1 or PGE2; the mechanical effects of the three prostaglandin synthetase inhibitors also were absent in the presence of elevated K+ or ouabain. The data are consistent with a hypothesis that, under conditions of our experiments, endogenous PGE has an effect on resting tension and spontaneous mechanical activity and on properties of the surface membrane of the guinea pig taenia coli.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1976

Endogenous prostaglandins and mechanical tension in canine trachealis muscle.

Prostaglandin E (PGS) is synthesized and released in isolated canine trachealis muscle (CTM), and the PGE threshold concentration for an effect on isometric tension is very low, indicating this prostaglandin is a most likely candidate for an endogenous prostaglandin that modulates or regulates tension. Prostaglandin F (PGF) is also released, but the threshold concentration for a mechanical effect is probably too high for endogenous PGF to have a direct effect on tension in this muscle. Indomethacin and aspirin, at concentrations commonly used to inhibit prostaglandin synthetase, had effects on tension, membrane potential, and membrane resistance, but these effects were not appropriate if their only action was to inhibit PGE or PGF concentration in CTM. Release of PGE from CTM was increased fourfold by treatment with carbachol, but even under this condition, where presumably cell [PGE] was increased, electrophysiological studies failed to give convincing evidence that the actions of indomethacin on mechanical tension were related to inhibition of PGE or PGF synthesis.

5,8,11,14-Eicosatetraynoic Acid↗