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Biomedical subjects

R P Rothlin

Publications and source records attributed to R P Rothlin.

14 recordsLinked to original sources
PubMed1998

Bradykinin B1 receptors in human umbilical vein: pharmacological evidence of up-regulation, and induction by interleukin-1 beta.

Bradykinin B1 receptor-mediated responses increase as a function of in vitro incubation in the human umbilical vein. When tissues were continuously treated with the protein synthesis inhibitor, cycloheximide, or with the protein trafficking inhibitor, brefeldin A, pEC50 and maximal response to the selective bradykinin B1 receptor agonist, des-Arg9-bradykinin, were significantly diminished. The anti-inflammatory steroid, dexamethasone, produced a rightward shift of the concentration-response curve to des-Arg9-bradykinin, without affecting the maximal response. Furthermore, lipopolysaccharide or recombinant human interleukin-1 beta potentiate the bradykinin B1-sensitized responses, showing a leftward shift of the concentration-response curve to des-Arg9-bradykinin, without modifying the maximal response. On the other hand, bradykinin B2 receptor-mediated responses were unaffected by continuous exposure to cycloheximide, dexamethasone or lipopolysaccharide. These results provide pharmacological evidence to support the view that the de novo synthesis of bradykinin B1 receptors is involved in the induction of vascular responses in the human umbilical vein. This up-regulation process seems to be selective for bradykinin B1 receptors. The inhibitory effect of dexamethasone and the potentiating actions of lipopolysaccharide and exogenous human recombinant interleukin-1 beta on des-Arg9-bradykinin-mediated responses, suggest the possible role of interleukin-1 beta in the bradykinin B1 receptor up-regulation phenomenon in human umbilical vein.

Anti-Inflammatory Agents↗
PubMed1997

Bradykinin B1 receptors in human umbilical vein.

The present study was undertaken to demonstrate the presence of bradykinin B1 receptors mediating contraction of human umbilical vein. The bradykinin B1 receptor selective agonist, des-Arg9-bradykinin, produced a dose-dependent contractile response of human umbilical vein rings. Furthermore, des-Arga-bradykinin-mediated response increased in a time-dependent manner in vitro. The maximal response to des-Arg9-bradykinin, expressed as percentage of the maximum elicited by serotonin, was: 10 +/- 2 at 15 min, 55 +/- 5 at 120 min and 80 +/- 3 at 300 min. Des-Arg9-bradykinin-mediated contractions were inhibited by the specific bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin which produced parallel shifts in the dose-response curve to the selective bradykinin B1 receptor agonist. Schild regression analysis of data established a pA2 value of 6.16 +/- 0.06. Kinin-induced contraction was not modified by pre-treatment with indomethacin (10 microM), a cyclo-oxygenase inhibitor. On the other hand, continuous exposure to the anti-inflammatory steroid dexamethasone (100 microM) or to the protein synthesis inhibitor cycloheximide (70 microM) largely prevented the sensitization to des-Arg9-bradykinin in incubated human umbilical vein rings. These results confirm the presence of bradykinin B1 receptors which mediate contraction in isolated human umbilical vein. These responses are up-regulated in a time- and protein synthesis-dependent process.

Anti-Inflammatory Agents↗
PubMed1995

[Amplification of contractile response by serotonin on noradrenaline in the human umbilical artery].

A progressive increase in plasma levels of serotonin (5-HT) during pregnancy has been reported. Furthermore, an increase in the concentration of noradrenaline (NA) has been described during labor. On the other hand, in different arteries it has been observed that minimal effective concentrations of 5-HT are able to produce an increase or "amplification" of the contractile response to a second agonist. From these reports, it seemed interesting to determine the existence of a synergistic interaction between 5-HT and NA in the human umbilical artery (HUA), and the probable mechanisms involved. Therefore, strips of HUA were incubated in Krebs solution at 37 degrees C and gassed with a mixture of CO2 (5%) and O2 (95%). The contractile isometric response was assessed. After a period of two hours, complete cumulative concentration-response curves to 5-HT and to NA were obtained. The maximal contractile response to NA was approximately 20% of the maximal response to 5-HT. In another series of experiments, the response to NA was enhanced by previous treatment with minimal effective doses of 5-HT (control response 0.24 +/- 0.06 g; "amplified" response 0.53 +/- 0.06 g, P < 0.01). This "amplified" response to NA was correlated with the degree of previous contraction with 5-HT, when the last was between 3 and 30% of the maximal response. However, precontractions higher than 40% abolished the responses to NA. In other experiments, the artery strips were incubated during thirty minutes with diltiazem 1 microM before agonists addition. In this condition, a decrease in the control and amplified response was observed. Therefore, we have shown the existence of an amplifying effect of 5-HT over the response to NA in the HUA, and we discuss the possible mechanisms involved and the possible clinical relevance in preeclampsia.

Humans↗
PubMed1993

Decrease of extracellular pH associated with the secretion of catecholamines induced by barium in perfused bovine adrenal medulla.

1. The possible modifications of extracellular pH produced during buffer-free 5 mM Ba2+ stimulation was studied in decorticated perfused bovine adrenal glands. 2. A significant and reversible drop of pH accompanied the release of catecholamines each time the tissue was exposed to a buffer-free 5 mM Ba2+ solution. 3. A progressive declination of the magnitude of this acidification associated with a gradual attenuation of the secretory response was observed consecutive to successive periods of Ba(2+)-stimulation. 4. D-600 (methoxyverapamil), in a concentration of 3 x 10(-4) M, markedly antagonized both Ba(2+)-induced secretory response and extracellular pH drop. 5. Perfusion of adrenal medulla for 4 min period with Locke solution buffered at pH 6.9, significantly and reversibly reduced the secretory response to 5 mM Ba2+ (pH 6.9) compared to a first control response obtained 35 min before at pH 7.4. 6. These results are compatible with the view that Ba(2+)-induced secretory activity is accompanied by the release of protons which could be involved in a local negative automodulatory mechanism of adrenomedullary secretion.

Adrenal Medulla↗
PubMed1972

Role of the -adrenoceptor in regulating noradrenaline overflow by nerve stimulation.

1. A study of the actions of phenoxybenzamine on transmitter overflow, neuronal and extraneuronal uptake of noradrenaline and in causing alpha-adrenoceptor blockade was carried out using the isolated cat nictitating membrane preparation.2. Phenoxybenzamine increased transmitter overflow elicited by nerve-stimulation at 10 Hz in a concentration dependent manner in the range 10(-8) to 10(-5) g/ml.3. Neuronal uptake of [(3)H]-noradrenaline was not inhibited by concentrations lower than 10(-6) g/ml of phenoxybenzamine. With 10(-7) g/ml of phenoxybenzamine a significant increase in transmitter overflow was obtained, although neuronal uptake of noradrenaline was not affected. Higher concentrations of phenoxybenzamine (10(-6) and 10(-5) g/ml) inhibited the neuronal uptake of noradrenaline and further increased transmitter overflow.4. Extraneuronal uptake of [(3)H]-noradrenaline was inhibited only with the highest concentration of phenoxybenzamine tested (10(-5) g/ml) and therefore appears to be unrelated to the effects on transmitter overflow.5. There was a significant correlation between the degree of alpha-adrenoceptor block produced by phenoxybenzamine and the increase in transmitter overflow obtained by nerve stimulation.6. These results indicate that phenoxybenzamine, in addition to increasing overflow by preventing reuptake of noradrenaline, may increase transmitter release.7. The possibility that phenoxybenzamine acts on alpha-adrenoceptors in the adrenergic nerve terminal is discussed. These receptors would be involved in a negative feedback mechanism regulating transmitter release.

Animals↗
PubMedDate not supplied

Acute effects of doxorubicin on chronotropic and inotropic mechanisms in guinea pig atria.

This study was designed to test the possible acute effects of doxorubicin (DOX) on isolated guinea pig atria incubated in Locke's solution. Different concentrations of DOX (10(-6) to 10(-4) M) were added to the medium 30 minutes before the concentration-response curves to noradrenaline and histamine were carried out. DOX (10(-4) M) significantly reduced spontaneous atrial rate. Atropine (10(-6) g/ml) was unable to modify this cardiodepressant effect. DOX (10(-4) M) produced a competitive beta blocking effect, shifting to the right the concentration-response curve to noradrenaline without altering the maximal chronotropic response. On the other hand, this anthracycline (10(-4) M) not only antagonized chronotropic responses to histamine, but significantly reduced the maximal effect mediated by this amine. Isolated left guinea pig atria electrically paced were used to determine the effects of DOX on positive inotropic activity promoted by noradrenaline and histamine. Similarly to what was observed in chronotropic experiments, DOX (10(-4) M) produced a competitive beta blocking action and a noncompetitive inhibition of the positive inotropic action developed by histamine. Lower concentrations of DOX failed to modify the chronotropic responses to both amines. However, after 60 minutes of incubation with DOX, 10(-5) M of this drug produced a shift to the right of the concentration-response curves to noradrenaline and histamine and depressed the maximal chronotropic response to these amines. These effects were not observed with 3 X 10(-6) M DOX. These results are compatible with the idea that a nonspecific interaction of DOX with cardiac beta and histaminergic receptors could be involved in the acute cardiotoxic mechanism produced by this anthracycline.

Adrenergic beta-Antagonists↗