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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin (5-HT), found in abundance in intestinal enterochromaffin cells, has been shown to be released in response to neural, humoral, and intraluminal stimuli but the mechanisms controlling release are poorly understood. The purpose of this study was to determine whether 5-HT release induced by the muscarinic agonist, methacholine, is mediated by enteric nerves or is a direct action at the mucosal cell level. We mounted rabbit mucosal sheets containing intact submucosal neural elements, but stripped of muscularis propria and myenteric plexus, in modified Ussing chambers and measured the release of 5-HT in response to 5 X 10(-5) M methacholine added to both mucosal and serosal surface bathing solutions, in the presence and absence of selective neural blockade with 1 X 10(-6) M tetrodotoxin. 5-HT release in control tissues (no drugs) as measured by radioimmunoassay was 25.7 +/- 6 ng/cm2/30 min (mean +/- SEM). In the presence of mucosal and serosal methacholine, total 5-HT release increased significantly (P less than 0.05) to 66.7 +/- 9 ng/cm2/30 min. When tetrodotoxin alone was applied, 5-HT release significantly increased to 55.2 +/- 9 ng/cm2/30 min compared to matched control. In the presence of tetrodotoxin, methacholine increased 5-HT release to 79.3 +/- 9 ng/cm2/30 min, which was significantly greater than with tetrodotoxin alone. These results provide evidence of an inhibitory neural regulation of basal 5-HT release since release increased in the presence of neural blockade. They also suggest that a muscarinic receptor at or near the enterochromaffin cells mediates mucosal 5-HT release since 5-HT is further increased by methacholine even in the presence of neural blockade.
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PMID:Serotonin release is mediated by muscarinic receptors on duodenal mucosal cells. 330 52

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

In the rat, stress activates the hypothalamus causing central adrenergic discharge with delivery of an alpha-adrenergic stimulus by the adrenergic hypothalamovagal pathway to the stomach. This stimulus controls intragastric blood flow and 5-HT release. In rats stressed pharmacologically by administration of intraperitoneal reserpine (0.1 mg/kg), the stimulated pathway releases gastric 5-HT which in turn significantly increases gastric acid secretion. Administration of intramuscular reserpine (0.1 mg/kg) every 24 hr for six weeks significantly (p less than 0.001 by Wilcoxon matched pairs signed-rank test) increased the basal acid output of the rat stomach (12 mumol/h +/- 0.5 vs 38.1 mumol/h +/- 2.4, mean +/- SEM) and produced duodenal ulceration in 83.3% of animals. Vagotomy completely protected the rat stomach against these effects. The data show that prolonged stress in the rat stimulates gastric acid secretion and produces duodenal ulceration.
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PMID:Stress, the adrenergic hypothalamovagal pathway, and the aetiology of chronic duodenal ulceration. 358 25

Neuroendocrine (endocrine-paracrine, APUD) cells of the guinea pig prostatic complex (prostate and coagulating gland) were studied at three age points (9-day-old weanlings, 11 to 12 week mature pre-breeders, and retired breeders) using serotonin immunocytochemistry for detection and subsequent morphometric analysis. Prostatic complex serotonin levels were determined for the same age groups using high performance liquid chromatography with electrochemical detection. The numbers of neuroendocrine (NE) cells in the prostatic complex of retired breeders was 1.42 +/- 0.29 NE cells/mm gland length (mean +/- SEM) and was increased nearly 24-fold when compared with mature pre-breeders with 0.06 +/- 0.03 NE cells/mm gland length and nearly 16-fold when compared with the weanlings with 0.09 +/- 0.04 NE cells/mm gland length. The increase in cell number in the retired breeders versus each of the other age groups was highly significant (p less than 0.001). The increase in NE cells appeared to take place exclusively in the prostate, whereas the number of NE cells in the coagulating gland were few and not significantly different in the three age groups. The number of urethral NE cells also appeared similar in all three age groups. The number of prostatic epithelial cells/gland length increased with age. The number of NE cells/100 prostatic epithelial cells was examined in the three age groups and the increase in retired breeders over the other two groups was still highly significant (p less than 0.001). Serotonin levels, which were measured for the whole prostatic complex, indicated a nearly 6-fold increase with age: retired breeders had 97.72 +/- 21.26 ng/g of wet tissue (mean +/- SEM) whereas mature pre-breeders had 17.1 +/- 2.88 ng/g of wet tissue (p less than 0.01). Weanling serotonin levels were not detectable. This dramatic age-related increase in prostatic NE cells and serotonin content could reflect a compensation for a decreased effectiveness of NE cell hormones, a nonfunctional primary hyperplasia, a hyperplasia secondary to endogenous hormonal or involutional changes or exogenous factors. Whatever the mechanism, this increase in prostatic NE cells with age is of great interest since human prostatic carcinoma and benign nodular hyperplasia are both strongly correlated with advanced age. Prostatic NE cells may, therefore, directly or indirectly be in the pathogenesis and/or evolution of these important pathologic processes.
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PMID:Age-related changes in the neuroendocrine (endocrine-paracrine) cell population and the serotonin content of the guinea pig prostate. 369 16

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

5-Hydroxytryptamine (5-HT; serotonin) turnover rate in dorsal raphe nucleus of the urethane-anesthetized rat was estimated by using the in vivo electrochemical detector to measure the decay of extraneuronal 5-hydroxyindole acetic acid (5-HIAA) after monoamine oxidase inhibition. Carbon paste electrodes were scanned by semiderivative voltammetry and revealed two peaks: one at +0.15 V and the other at +0.25 V. The higher potential peak is composed primarily of the 5-HT metabolite 5-HIAA. After administration of pargyline, 75 mg/kg i.p., this peak declined exponentially. Regression analysis of these data by an exponential decay model yielded the fractional rate constant 0.82 +/- 0.06 h-1 (mean +/- SEM). This rate constant of 5-HIAA disappearance measured by in vivo electrochemistry is identical to the rate constant found by others measuring 5-HIAA disappearance by direct tissue assay methods. In animals not treated with pargyline, tissue 5-HIAA concentrations in the dorsal raphe nucleus were measured by HPLC with electrochemical detection. The average 5-HT turnover rate calculated as the product of the fractional rate constant and steady-state tissue 5-HIAA concentration was 12.6 nmol/g/h. These results demonstrate that electrochemical detection of extraneuronal 5-HIAA combined with monoamine oxidase inhibition can be used to measure neurotransmitter turnover in vivo in a discrete brain region.
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PMID:Measurement of serotonin turnover rate in rat dorsal raphe nucleus by in vivo electrochemistry. 620 May 72

Although numerous studies have provided indirect evidence for enhanced platelet activity in sickle cell anaemia, little attention has been directed to examination of platelet alpha and dense granule release in the sickling disorders. We simultaneously measured by radioimmunoassay plasma levels of the alpha granule constituents beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) in 43 children with sickle cell anaemia in steady state and 24 patients during severe vaso-occlusive crisis. beta-TG levels during steady state (50 +/- 3.6 ng/ml, mean +/- SEM) were greater (P less than 0.001) than in normal controls (36 +/- 1.6), but there was no additional significant rise during crisis (55 +/- 5.9). PF4 levels were similar (P = 0.12) in both steady state (10 +/- 1.2 ng/ml) and crisis (9.3 +/- 2.3) to those of normal controls (6.0 +/- 0.8). The similarity of beta-TG/PF4 ratios in normal and sickle cell anaemia patients as well as the positive correlation (P less than 0.05) between platelet count and beta-TG and PF4 suggested that an artefactual in vitro platelet activation was responsible for some of the observed increased beta-TG and PF4 levels. Further evidence against enhanced platelet activity in these sickle cell patients included normal intraplatelet content of the dense granule constituent 5-HT and a normal ATP/ADP ratio. From this data we conclude that platelet activation in children with sickle cell anaemia appears minimal.
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PMID:Evidence against enhanced platelet activity in sickle cell anaemia. 622 55

The serotonin (5-hydroxytryptamine, 5-HT) antagonist, ketanserin, has a high affinity for 5-HT2-receptors but it also binds to alpha 1-adrenoceptors. The compound (10 mg i.v.) lowered mean arterial pressure by 22% +/- 2% (mean +/- SEM, p less than 0.001) in 30 patients with essential hypertension. Measurements of heart rate, cardiac output, cardiac filling pressures, forearm blood flow, renal blood flow, and glomerular filtration rate revealed a hemodynamic pattern compatible with vasodilation of both resistance and capacitance vessels. This was accompanied by moderate reflex cardiostimulation. Ketanserin did not alter the pressor effect of bolus injections of (-)-phenylephrine hydrochloride (25, 50, 100, and 200 micrograms i.v.). Ketanserin also had a distinct hypotensive effect in four normotensive patients with autonomic insufficiency due to an efferent sympathetic lesion, who were unresponsive to phentolamine (20 mg i.v.). Thus, ketanserin in the dose we have used appears to lower blood pressure independently of alpha 1-adrenoceptor blockade. On the other hand, in patients with essential hypertension the antihypertensive effect of ketanserin was blunted by pretreatment with prazosin (12 mg/day). Therefore, a certain degree of alpha 1-adrenergic tone seems to be required for the compound to exert its full antihypertensive action. The findings are indirect evidence for a role of 5-HT in the maintenance of increased vascular resistance in essential hypertension. This may be related, at least in part, to the alleged amplifying effect of 5-HT on alpha 1-adrenoceptor-mediated vasoconstriction.
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PMID:5-HT, alpha-adrenoceptors, and blood pressure. Effects of ketanserin in essential hypertension and autonomic insufficiency. 631 78

The serotonin (5-hydroxytryptamine, 5-HT) content of tissue compartments in the medicinal leech, Hirudo medicinalis, was measured by means of high-pressure liquid chromatography coupled with electrochemical detection (HPLC-EC). Each segmental ganglion contains 21.3 +/- 2.9 (9) pmol 5-HT [X +/- SEM (N)]. The pharynx contains 7.1 +/- 1.1 (9) pmol 5-HT/mg wet weight; the salivary glands 3.2 +/- 0.9 (10), ventral body wall 2.0 +/- 0.2 (11), and vasofibrous tissue 1.2 +/- 0.2 (11). The blood of hungry leeches contains 8.7 +/- 1.9 (7) nM 5-HT while that of well-fed leeches is 2.2 +/- 0.4 (6) nM. Leeches were injected with the cytotoxic analog of serotonin, 5,7-dihydroxytryptamine (5,7-DHT) producing selective lesions of the peripherally projecting serotonin-containing neurons, and which in turn abolished their feeding behavior. The serotonin content of the pharynx and ganglia of these toxin-treated leeches were lowered significantly. The serotonin levels within the body wall and salivary glands were not altered significantly by the toxin treatment, but the levels within the vasofibrous tissue and blood were elevated substantially.
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PMID:Quantitative effects of a neurotoxin upon serotonin levels within tissue compartments of the medicinal leech. 650 56

In 14 patients with coronary heart disease the effect of long-term treatment (mean 16 months, range 12-33) with alprenolol on platelet function and fibrinolytic activity was studied. While on the beta-blocker and two weeks after gradual withdrawal of it, the patients performed a bicycle-ergometer test and blood samples were obtained before and following exercise. Pre-exercise fibrinolytic activity, assessed by the euglobulin clot lysis time, was 183 +/- 27 min (mean +/- SEM) while on alprenolol as compared to 111 +/- 18 min (p less than 0.01) after its withdrawal. Activation of fibrinolysis following exercise was not significantly influenced by alprenolol. In patients treated with alprenolol, the pre-exercise threshold level of ADP, producing platelet aggregation was 3.3 muM (geometric mean) and 5.1 muM after stopping treatment (p less than or equal to 0.05). In patients receiving the beta-blocker, the ADP- threshold value dropped from 3.3 muM before exercise to 2.3 muM immediately after exercise (not significant). The corresponding values after withdrawal of alprenolol were 5.1 muM and 2.7 muM (p less than or equal to 0.02). Adrenaline - stimulated aggregation was not significantly influenced by alprenolol. Serotonin release from platelets following maximal ADP- and adrenaline stimuli was not significantly changed by exercise in patients on beta-blockade. After stopping treatment, ADP-induced serotonin release was 22 +/- 4.1% before and 15 +/- 4.7% after exercise (p less than 0.02). the corresponding values using the adrenaline stimulus were 29 +/- 5.7% and 17 +/- 4.7% (p less than 0.05). It is suggested that during physical stress alprenolol may protect platelets against aggregatory stimuli.
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PMID:Effect of long-term beta-blockade with alprenolol on platelet function and fibrinolytic activity in patients with coronary heart disease. 703 Jul 49


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