1. 5-HT inhibits spontaneous fluid secretion as well as stimulated secretion with secretin (cAMP mediated) or ACh (Ca2+ mediated) in the isolated guinea pig pancreatic ducts. 2. The inhibitory effect of 5-HT is reversible and is dependent on the concentration in the range 0.01-0.1 microM, which is much lower than those that affect intestinal motility and secretion. 3. The 5-HT3 receptor in duct cells appears to mediate the inhibitory effect of 5-HT. 4. [Ca2+]i is unlikely to mediate the inhibitory effect of 5-HT.
5-Methoxytryptamine/pharmacology ; Acetylcholine/pharmacology ; Animal ; Calcium/metabolism ; Guinea Pigs ; Pancreatic Ducts/metabolism* ; Pancreatic Ducts/drug effects ; Secretin/pharmacology ; Serotonin/pharmacology ; Serotonin/metabolism* ; Serotonin/analogs & derivatives* ; Vasodilator Agents/pharmacology

AIMTo explore the modulation of 5-HT on GABA-activated current (I(GABA)) in the membrane of rat dorsal root ganglion (DRG) neurons and its mechanism.

METHODSRat DRG neurons were isolated mechanically and enzymatically, on which whole-cell patch clamp recording and repatch technique for intracellular dialysis were performed.

RESULTSIn the majority of neurons examined (92.0%, 69/75) GABA induced a concentration-dependent inward current. In neurons sensitive to GABA preapplication of 5-HT produced potentiation effect (82.6% , 57/69) on I(GABA). Preapplication of 5-HT at concentrations of 1 x 10(-6), 1 x 10(-5), 1 x 10(-4) and 1 x 10(-3) mol x L(-1) potentiated I(GABA) by (35 +/- 8)% (n=8), (47 +/- 11)% (n=10), (65 +/- 17)% (n=9) and (75 +/- 18)% (n=11), respectively. This effect was mimicked by alpha-methyl-5-HT (1 x 10(-6) mol x L(-1)), a specific 5-HT2 receptor agonist, and reversed by cyproheptadine, a selective 5-HT2 receptor antagonist. The potentiation of I(GABA) by 5-HT was irrespective to whether the I(5-HT) presents or not in a subset of neurons. The concentration-response curves for GABA before and after pretreatment with 5-HT manifested the same threshold value and similar EC50 (2.0 x 10(-5) and 1.9 x 10(-5) mol x L(-1), respectively) , while the maximal value of I(GABA) for the latter was 33.6% higher than that for the former. Intracellular dialysis with GDP-beta-S or H-7 abolished the potentiation of I(GABA) by 5-HT, while H-9 did not.

CONCLUSION5-HT can potentiate GABA-activated current via PKC-dependent phosphorylation of GABA(A) receptor following the activation of 5-HT2 receptor.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine ; pharmacology ; Animals ; Cyproheptadine ; pharmacology ; Female ; Ganglia, Spinal ; cytology ; physiology ; Male ; Membrane Potentials ; drug effects ; Neurons ; physiology ; Patch-Clamp Techniques ; Protein Kinase C ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT2 ; Serotonin ; analogs & derivatives ; pharmacology ; Serotonin 5-HT2 Receptor Agonists ; Serotonin 5-HT2 Receptor Antagonists ; Signal Transduction ; gamma-Aminobutyric Acid ; pharmacology

OBJECTIVETo compare the incidences of sexual dysfunction induced by mirtazapine and SSRI in the treatment of patients with depression.

METHODSUsing key-word retrieval from the compact disks of the Chinese biological medicine (CBM) data base, we analyzed the rates of sexual dysfunction from the published clinical control trials on depression treated with mirtazapine and SSRI by applying the fixed effects model (FEM) of evidence-based medicine (EBM).

RESULTSAmong 1108 cases in 14 studies, there were 5 cases of mirtazapine-induced and 106 cases of SSRI-induced sexual dysfunction, accounting for 0.90% and 19.2% respectively, OR = 0.07 (95% CI: 0.04-0.14), Z = 8.03, P < 0.01.

CONCLUSIONSSRI is far more likely to induce sexual dysfunction than mirtazapine in the treatment of depression.

Antidepressive Agents, Tricyclic ; adverse effects ; Depressive Disorder ; drug therapy ; Erectile Dysfunction ; chemically induced ; Humans ; Male ; Mianserin ; adverse effects ; analogs & derivatives ; Serotonin Uptake Inhibitors ; adverse effects

Methylation, a methyl group-consuming reaction, plays a key role in the degradation (i.e., inactivation) of monoamine neurotransmitters, including catecholamines, serotonin and histamine. Without labile methyl groups, the methylation-mediated degradation cannot take place. Although high niacin (nicotinic acid and nicotinamide) intake, which is very common nowadays, is known to deplete the body's methyl-group pool, its effect on monoamine-neurotransmitter degradation is not well understood. The aim of this article was to investigate the effect of excess nicotinamide on the levels of plasma serotonin and histamine in healthy subjects. Urine and venous blood samples were collected from nine healthy male volunteers before and after oral loading with 100 mg nicotinamide. Plasma N(1)-methylnicotinamide, urinary N(1)-methyl-2-pyridone-5-carboxamide (2-Py), and plasma betaine levels were measured by using high-performance liquid chromatography (HPLC). Plasma concentrations of choline, serotonin and histamine were measured using commercial kits. The results showed that the plasma N(1)-methylnicotinamide level and the urinary excretion of 2-Py significantly increased after oral loading with 100 mg nicotinamide, which was accompanied with a decrease in the methyl-group donor betaine. Compared with those before nicotinamide load, five-hour postload plasma serotonin and histamine levels significantly increased. These results suggest that excess nicotinamide can disturb monoamine-neurotransmitter metabolism. These findings may be of significance in understanding the etiology of monoamine-related mental diseases, such as schizophrenia and autism (a neurodevelopmental disorder).
Betaine ; blood ; Choline ; blood ; Chromatography, High Pressure Liquid ; Histamine ; blood ; Humans ; Male ; Niacinamide ; administration & dosage ; analogs & derivatives ; blood ; Pyridones ; urine ; Serotonin ; blood

BACKGROUNDSarpogrelate is a selective 5-hydroxytryptamine (5-HT) receptor subtype 2A antagonist which blocks 5-HT induced platelet aggregation and proliferation of vascular smooth muscle cells. We compared the efficacy of sarpogrelate-based dual antiplatelet therapies for the prevention of restenosis and target lesion revascularization (TLR) rates comparing with that of clopidogrel after percutaneous endovascular interventions (EVIs) of femoropopliteal (FP) arterial lesions.

METHODSThis prospective, multicenter, randomized clinical trial recruited a total of 120 patients with successful EVI of FP lesions at seven centers across China between January 2011 and June 2012. Patients were randomized to receive either sarpogrelate (100 mg trice daily for 6 months, n = 63) or clopidogrel (75 mg once daily for 6 months, n = 57). All patients also received oral aspirin (100 mg once daily for 12 months). Clinical follow-up was conducted up to 12 months postprocedure.

RESULTSThere was no significant difference between the two groups in basic demographic data. The restenosis rate was higher in the clopidogrel group (22.80%) than in sarpogrelate group (17.50%), but there was no significant difference between these two groups (P = 0.465). The TLR rate, ipsilateral amputation rate, mortality in all-cause and bleeding rate were also similar in the two groups (P > 0.05).

CONCLUSIONSAspirin plus sarpogrelate is a comparable antithrombotic regimen to aspirin plus clopidogrel after EVI of FP arterial lesions. Dual antiplatelet therapies might play an important role in preventing restenosis after successful EVI of FP lesions.

Aged ; Arterial Occlusive Diseases ; drug therapy ; Female ; Fibrinolytic Agents ; therapeutic use ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Peripheral Vascular Diseases ; drug therapy ; Popliteal Artery ; drug effects ; pathology ; Serotonin Antagonists ; therapeutic use ; Succinates ; therapeutic use ; Ticlopidine ; analogs & derivatives ; therapeutic use

AIMTo investigate the impact of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on the change of cerebral blood flow(CBF) induced by 5-HT or KCl in rats.

METHODSThe CBF in rats was measured by a Laser-Doppler flowmeter. The cranial window field was superfused with artificial cerebral spinal fluid containing TMB-8, 5-HT or KCl.

RESULTS12.5, 25 and 50 mumol.L-1 TMB-8 showed no significant effect on rest CBF in rats. 12.5, 25 and 50 mumol.L-1 TMB-8 apparently inhibited the decline of CBF evoked by 1 or 2 mumol.L-1 5-HT. When persistent reduction of CBF were evoked by 1 mumol.L-1 5-HT, TMB-8 markedly increased the CBF in a concentration-dependent manner. The reduction of CBF induced by 20 or 40 mmol.L-1 KCl was also suppressed by 12.5, 25 and 50 mumol.L-1 TMB-8. While persistent reduction of CBF was evoked by 20 mmol.L-1 KCl. TMB-8 markedly increased the CBF in a concentration-dependent manner.

CONCLUSIONThese results indicate that TMB-8 is effective in preventing and treating the reduction of CBF induced by 5-HT or KCl, and improved the supply of blood in rat brain during ischemia.

Animals ; Brain ; blood supply ; drug effects ; Calcium Channel Blockers ; pharmacology ; Drug Interactions ; Gallic Acid ; analogs & derivatives ; pharmacology ; Potassium Chloride ; antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Regional Blood Flow ; drug effects ; Serotonin Antagonists ; pharmacology

5-Hydroxytryptamine 2C (5-HT) receptor is one of the major targets of anti-obesity agents, due to its role in regulation of appetite. In the present study, the 70% EtOH extract of the roots of Bupleurum chinense was revealed to have agonistic activity on 5-HT receptor, and the subsequent bioassay-guided isolation led to identification of several saikosaponins as the active constituents with 5-HT receptor agonistic activity in vitro and anti-obesity activity in vivo. The new compound, 22-oxosaikosaponin d (1), was determined by extensive spectroscopic analyses (HR-ESI-MS, IR, and 1D and 2D NMR). The primary structure-activity relationship study suggested that the intramolecular ether bond between C-13 and C-28 and the number of sugars at C-3 position were closely related to the 5-HT receptor agonistic activity. Saikosaponin a (3), the main saponin in B. chinense, showed obviously agonistic activity on 5-HT receptor with an EC value of 21.08 ± 0.33 μmol·Lin vitro and could reduce food intake by 39.1% and 69.2%, and weight gain by 13.6% and 16.4%, respectively, at 3.0 and 6.0 mg·kgin vivo. This investigation provided valuable information for the potential use of B. chinense as anti-obesity agent.
Animals ; Anti-Obesity Agents ; chemistry ; isolation & purification ; pharmacology ; Biological Assay ; Bupleurum ; chemistry ; Male ; Oleanolic Acid ; analogs & derivatives ; chemistry ; isolation & purification ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Saponins ; chemistry ; isolation & purification ; pharmacology ; Serotonin 5-HT2 Receptor Agonists ; chemistry ; isolation & purification ; pharmacology ; Structure-Activity Relationship