Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is very important to find suitable reaction conditions to attain a high specific binding (specific/total binding) in the receptor binding study. Membrane homogenates of pig choroid plexus are known to have exclusively serotonin (5-hydroxytryptamine, 5-HT) receptor of the subtype 5-HT1c. In this study, we used the membrane preparation of pig choroid plexus tissue and the specific binding of [3H]5-HT was 72-84% to serotonin receptor subtype 5-HT1c, as defined by the inhibition of 1 uM 5-HT, when a radioligand concentration of 0.5 nM of [3H]5-HT was used in the assay. Analysis of the properties of specific [3H]5-HT binding in pig choroid plexus tissue membrane preparation revealed linear Scatchard plots. In Tris-HCl buffer without CaCl2, pargyline or ascorbic acid, high average of affinity dissociation constant (Kd) of 1.3 +/- 0.2 nM (SEM, n = 4) and also a high average of receptor density (Bmax) of 284 +/- 12 fmol/mg of protein were found. Pig choroid plexus proves to be a good material for 5-HT1c receptor binding study.
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PMID:Serotonin (5-HT1c) receptors in pig choroid plexus. 184 41

Superfusion of hemisected lumbar spinal cord of the neonatal rat with solutions containing 10(-6) to 10(-3) M 5-hydroxytryptamine (5-HT) elicited depolarizations of graded amplitude which were recorded from motorneurons through a ventral root. Maximum responses (amplitude 1.0 +/- 0.1 mV, mean +/- SEM, n = 30) were evoked by 10(-4) M 5-HT. Repeated concentration-response curves could be determined from the same preparation. There was no involvement of 5-HT2 receptors in the depolarizing response to 5-HT, since neither ritanserin nor ICI 169, 369 showed any antagonist action. Amongst agents with activity at 5-HT1A sites, the selective 5-HT1A receptor agonist, 8-hydyroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), neither mimicked the action of 5-HT nor antagonised it, while spiperone (10(-8)-10(-7 M) antagonised responses to 5-HT in a concentration-related manner. Responses to 10(-4) M noradrenaline, used as a control depolarizing agent, were unaffected by spiperone. The onset of blockade by spiperone was slow, 1 hr being required for equilibration of the tissue with antagonist. The blockade was surmountable by larger concentrations of 5-HT. Concentration-response curves to 5-HT were shifted to the right in an approximately parallel manner by spiperone. The dose ratios measured from these curves at the EC50 level, yielded an apparent pA2 of 8.24 +/- 0.14 (mean +/- SEM, n = 15), although the Schild plot of the data had a slope less than unity. The lack of activity of the selective 5-HT1B receptor agonist, RU 24969, and the 5-HT1B receptor antagonists, (+/-) cyanopindolol and quipazine, indicated that 5-HT1B receptors were not involved in the 5-HT response of motorneurones to 5-HT. Mesulergine, metergoline and cyproheptadine also antagonised responses of motorneurones to 5-HT, producing a surmountable blockade. Mesulergine (10(-8), 3 x 10(-8) and 10(-7) M caused a progressive rightward shift of the concentration-response curves, but 10(-7) M depressed the maximum response to 5-HT. Responses to noradrenaline were not affected by these concentrations of mesulergine. The apparent pA2 for blockade of 5-HT responses by mesulergine, calculated from experiments in which there was a parallel displacement of the concentration-response curves, was 8.75 +/- 0.11 (mean +/- SEM, n = 10).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:5-Hydroxytryptamine depolarizes neonatal rat motorneurones through a receptor unrelated to an identified binding site. 275 65

With a multibarrel assembly combining one carbon fiber micropipette as recording electrode and 6 pipettes for microiontophoretic application of drugs, the activity of neurons in the preoptic and anterior hypothalamic (POAH) region was extracellularly recorded in situ in conscious ducks implanted chronically with a device permitting hypothalamic thermal stimulation. Among 355 neurons 17% were identified as warm-responsive (warm units) and 20% as cold-responsive (cold units). In 58 warm and 56 cold units control discharge rates at 40 degrees C local temperature (F40) and temperature coefficients (delta F/delta T) were determined and presented as means +/- SEM. The F40 values of warm units (35.2 +/- 2.3 Imp . s-1) were significantly higher than of cold units (16.3 +/- 1.8 Imp . s-1). The delta F/delta T values (+1.77 +/- 0.15 and -1.77 +/- 0.19 Imp . s-1 . degree C-1) of warm and cold units were not different in absolute terms. In pilot experiments either activation or inhibition by lowering whole-body temperature was observed in both warm and cold units. Microiontophoretic application of one or more of the amines acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and noradrenaline (NA) to warm and cold units revealed differences in their responsiveness to ACh, which more consistently stimulated cold units. NA inhibited the majority of warm units; 5-HT stimulated the majority of cold units. In both warm and cold units NA and ACh differed in their actions, with the latter amine more consistently producing activation.
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PMID:Thermal characterization and transmitter analysis of single units in the preoptic and anterior hypothalamus of conscious ducks. 289 54

The role of 5-HT3 receptors in the biphasic vasodilator response to serotonin (5-hydroxytryptamine; 5-HT) was investigated in the forearm of 7 young healthy volunteers (aged 22-32 years). Single dose infusions of 5-HT (1 ng/kg/min) and of acetylcholine (ACh, 500 ng/kg/min) were administered into the brachial artery. Subsequently combined infusions of 5-HT together with the selective 5-HT3 receptor antagonist ICS 205-930 (350 and 700 ng/kg/min), and ACh together with ICS 205-930 (700 ng/kg/min) were given. After a pause of at least 1 hour the single infusions of 5-HT and ACh were repeated. Subsequently, 5-HT and ACh were infused together with atropine (100 ng/kg/min). Forearm blood flow (FBF) was measured by R-wave triggered venous occlusion plethysmography. Heart rate (HR) and i.a. blood pressure (BP) were recorded semi-continuously. None of the drugs in the doses used did induce systemic hemodynamic effects. After an initial rapid transient increase in FBF of 316 +/- 55%, 5-HT elicited a persistent increase in FBF of 90 +/- 22% (mean +/- SEM, p less than 0.05 for both). ACh induced a monophasic vasodilatation of 475 +/- 123% (p less than 0.05). Both the initial transient and the persistent dilatator response to 5-HT were attenuated by ICS 205-930 350 ng/kg/min (p = 0.057, n = 5) and 700 ng/kg/min (p less than 0.05, n = 7). The highest dose of ICS 205-930 did not significantly influence the dilatator response to ACh. Atropine abolished the ACh induced vasodilatation (p less than 0.05), but did not influence the biphasic dilatator response to 5-HT. Thus the 5-HT induced biphasic vasodilatation was antagonized by ICS 205-930, indicating that this response was mediated by 5-HT3 receptor activation. The fact that atropine did not influence the vascular response to 5-HT suggests that 5-HT did not induce vascular relaxation indirectly by the release of ACh from cholinergic nerve endings.
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PMID:Serotonin induced vasodilatation in the human forearm is antagonized by the selective 5-HT3 receptor antagonist ICS 205-930. 318 2

Experiments to explore human platelet protein phosphorylation changes and 5-hydroxytryptamine (5-HT) secretion after challenge with cotton bract tannin were performed. Quantitative changes in sodium phosphate phosphorus 32 incorporation in two platelet proteins of 19 kilodaltons (kd) and 47 kd were assessed by measuring protein band densities on autoradiographs of dried polyacrylamide gels. Secretion of 5-HT was assessed by 14C-5-HT release. Results show that tannin causes increases in phosphorylation of discrete platelet proteins that begin in less than 2 seconds. These increases are maximal in 1 minute for the 47 kd protein and in 3 minutes for the 19 kd protein. Fifty percent of maximum response required less than 2 seconds for both of these proteins, and 50% of maximum 5-HT secretion required 48 seconds. Dose-response studies comparing 0 to 50 micrograms/ml tannin with 0 to 1 U/ml human alpha-thrombin showed that tannin caused 5-HT secretion and protein phosphorylation changes that were very similar to those induced by human alpha-thrombin. Fifty micrograms per milliliter of tannin caused increases in 19 kd protein phosphorylation and 47 kd protein phosphorylation to 312% +/- 34% (SEM) and 204% +/- 13% of control, respectively (n = 14). One unit per milliliter of thrombin induced changes of 350% +/- 40% and 221% +/- 17% of control in the 19 kd and 47 kd proteins, respectively. Release of 5-HT by tannin and thrombin was 61% +/- 3% and 69% +/- 3% of total cellular 5-HT, respectively. Indomethacin had little inhibitory effect on activation by these two different agents.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein phosphorylation during tannin-mediated activation of human platelets. 334 45

Because experimental lung injury is associated with decreased removal of 3H-prostaglandin E1 (3H-PGE1) and 14C-5-hydroxytryptamine (14C-5-HT), we questioned whether a similar reduction would be evident in patients with the adult respiratory distress syndrome (ARDS). Accordingly, we measured, by indicator dilution techniques, pulmonary removal of 3H-PGE1 and 14C-5-HT in 11 patients undergoing cardiopulmonary bypass surgery in whom respiratory function was essentially normal, and compared them with similar measurements in 9 patients who had ARDS. In addition, we made 5 successive measurements of lung removal functions in the bypass group of patients during the 48-h period after the first measurement. These measurements were made before and 4 times (within 48 h) after the first measurement. Before bypass, removal of 3H-PGE1 and 14C-5-HT was 78 +/- 2 SEM and 89 +/- 2%, respectively; these did not change during the subsequent 48 h. Therefore, we compared prebypass values in this group with measurements made in patients with ARDS. The latter group had significantly decreased removal of 3H-PGE1 and 14C-5-HT (values were 66 +/- 3 and 72 +/- 5%, respectively). We suggest that these changes reflect a diffuse functional injury to the endothelium similar to that seen after acute lung injury in laboratory animals.
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PMID:Depressed prostaglandin E1 and 5-hydroxytryptamine removal in patients with adult respiratory distress syndrome. 353 86

The blocking action of MDL 72222 (1 alpha H, 3 alpha, 5 alpha H-tropan-3-yl-3, 5-dichlorobenzoate at 5-hydroxytryptamine (5-HT) receptors on nodose (NG) and superior cervical ganglia (SCG) has been investigated further. The sucrose-gap technique was used to record potential changes from populations of neurones. The surmountable blockade induced by small concentrations of the antagonist was quantified and the blocking potency compared with that of a number of other compounds. In nodose ganglia three 4-5 point dose-response (DR) curves were established, using bolus injections of 5-HT (5-80 nmol). The mean amplitude of the response to 80 nmol was 4.18 +/- 0.53 mV and the ED50 was 18.2 nmol. Second and 3rd dose-response curves showed small displacements to the right, indicating a slight reduction in sensitivity. In superior cervical ganglia responsiveness was less. Amounts of 5-HT ranging from 20 to 320 nmol evoked dose-related depolarizations. The mean amplitude of the response evoked by 320 nmol 5-HT was 1.7 +/- 0.14 mV. Three 4-5 point dose-response curves could be elicited from a single ganglion. The ED50 was 55.8 nmol. Initial, 2nd and 3rd dose-response curves could be superimposed, there being no significant rightward shift. The results confirm that MDL 72222 is a potent, selective antagonist at 5-HT receptors in nodose and superior cervical ganglia. In the nodose ganglion, after equilibration for 1 hr with 10(-8) or 10(-7) M MDL 72222, dose-response curves for 5-HT showed rightward, parallel shifts. In contrast, 10(-6) M MDL 72222 or prolonged exposure (3-4 hr) to 10(-8), 10(-7) or 10(-6) M caused larger rightward shifts of the dose-response curves and depressed the maximum responses. In the superior cervical ganglion, equilibration for 1 hr with concentrations of 10(-8) or 10(-7) M produced effects on the dose-response curves similar to those seen in the nodose ganglion, but longer exposures (3-4 hr) did not depress the maximum. Apparent pA2 values were determined from individual experiments on both the nodose and superior cervical ganglia, where MDL 72222 (10(-7) M or less, for 1 hr) caused parallel or near parallel shifts of dose-response curves. In the nodose ganglion the apparent pA2 was 7.7 +/- 0.1, while in the superior cervical ganglion it was 7.8 +/- 0.1 (mean +/- SEM). The nature of the blockade induced by prolonged exposures or by concentrations greater than 10(-7) M is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Further studies on the blockade of 5-HT depolarizations of rabbit vagal afferent and sympathetic ganglion cells by MDL 72222 and other antagonists. 356 18

A study was made of the pharmacological and electrophysiological properties of pieces of small intrapulmonary arteries (100-450 micron I.D.) taken from children with cardiac defects that caused the pulmonary circulation to be exposed to an abnormally high perfusion pressure. The sensitivity of the arterial smooth muscle to the constrictor agonists acetylcholine and 5-hydroxytryptamine was similar to that reported for adult pulmonary arteries. Norepinephrine or histamine caused little or no constriction, although both these substances have been reported to be powerful constrictors of adult pulmonary arteries. The electrophysiological properties were similar to those of the smooth muscle of systemic arteries. The mean resting membrane potential was -6.12 mV +/- 1.29 (SEM n = 16). Stimulation of the perivascular nerves produced excitatory junction potentials, but no smooth muscle action potentials were recorded. Histochemical investigation revealed catecholamine containing nerve fibres around all intrapulmonary arteries down to 40 micron I.D.
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PMID:An in vitro study of the pharmacological and electrophysiological properties and the adrenergic innervation of small pulmonary arteries from children with pulmonary hypertension. 376 88

Outer diameter of the isolated pig coronary artery was measured under isotonic conditions using a sonomicrometer, and tension development of a ring preparation was assessed isometrically by a strain gauge transducer. Potassium chloride (KCl), acetylcholine (ACh) and 5-hydroxytryptamine dose-dependently reduced the coronary outer diameter. There was a direct linear relation between the reduction of diameter and tension development by these agents (r = 0.91, n = 15, p less than 0.001). KCl was one of the most potent vasoconstrictors tested and reduced the outer diameter by 35 +/- 1% (n = 15, mean +/- SEM) at 120 mM. ACh produced a transient increase in isometric tension and the reduction of the coronary diameter by ACh was smaller than that seen with KCl, even with a dose which produced the similar peak level of isometric tension by KCl and ACh. It is concluded that changes in the coronary diameter do closely correlate with those in tension development, however, the reduction of coronary diameter after exposure to vasoconstrictive agents is less in phasic than tonic contraction. The latter evidence suggests the importance of both the strength and duration of active vasoconstriction in eliciting coronary spasm.
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PMID:Vasoconstrictor agents correlatively alter diameter and tension development in isolated pig coronary arteries. 400 28

Primary astrocyte cultures prepared from the cerebral cortices of neonatal rats showed significant accumulation of serotonin (5-hydroxytryptamine; [3H]-5-HT). At concentrations in the range of 0.01 to 0.7 microM [3H]-5-HT, this uptake was 50 to 85% Na+ dependent and gave a Km of 0.40 +/- 0.11 microM [3H]-5-HT and a Vmax of 6.42 +/- 0.85 (+/- SEM) pmol of [3H]-5-HT/mg of protein/4 min for the Na+-dependent component. In the absence of Na+ the uptake was nonsaturable. Omission of the monoamine oxidase inhibitor pargyline markedly reduced the Na+-dependent component of [3H]-5-HT uptake but had a negligible effect on the Na+-independent component. This suggest significant oxidative deamination of serotonin after it has been taken up by the high affinity system, followed by release of its metabolite. We estimated that this system enabled the cells to concentrate [3H]-5-HT up to 44-fold at an external [3H]-5-HT concentration of 10(-7) M. Inhibition of [3H]-5-HT uptake by a number of clinically effective antidepressants was also consistent with a specific high affinity uptake mechanism for 5-HT, the order of effectiveness of inhibition being chlorimipramine greater than fluoxetine greater than imipramine = amitriptyline greater than desmethylimipramine greater than iprindole greater than mianserin. Uptake of [3H]-5-HT was dependent on the presence of Cl- as well as Na+ in the medium, and the effect of omission of both ions was nonadditive. Varying the concentration of K+ in the media from 1 to 50 mM had a limited effect on [3H]-5-HT uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Kinetics and autoradiography of high affinity uptake of serotonin by primary astrocyte cultures. 402 Apr 24


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