Prophylactic effects of asiaticoside-based standardized extract of Centella asiatica (L.) Urban leaves on experimental migraine: Involvement of 5HT1A/1B receptors / 中国天然药物

The present study aimed at evaluation of prophylactic efficacy and possible mechanisms of asiaticoside (AS) based standardized extract of Centella asiatica (L.) Urban leaves (INDCA) in animal models of migraine. The effects of oral and intranasal (i.n.) pretreatment of INDCA (acute and 7-days subacute) were evaluated against nitroglycerine (NTG, 10 mg·kg(-1), i.p.) and bradykinin (BK, 10 μg, intra-arterial) induced hyperalgesia in rats. Tail flick latencies (from 0 to 240 min) post-NTG treatment and the number of vocalizations post-BK treatment were recorded as a measure of hyperalgesia. Separate groups of rats for negative (Normal) and positive (sumatriptan, 42 mg·kg(-1), s.c.) controls were included. The interaction of INDCA with selective 5-HT1A, 5-HT1B, and 5-HT1D receptor antagonists (NAN-190, Isamoltane hemifumarate, and BRL-15572 respectively) against NTG-induced hyperalgesia was also evaluated. Acute and sub-acute pre-treatment of INDCA [10 and 30 mg·kg(-1) (oral) and 100 μg/rat (i.n.) showed significant anti-nociception activity, and reversal of the NTG-induced hyperalgesia and brain 5-HT concentration decline. Oral pre-treatment with INDCA (30 mg·kg(-1), 7 d) showed significant reduction in the number of vocalization. The anti-nociceptive effects of INDCA were blocked by 5-HT1A and 5-HT1B but not 5-HT1D receptor antagonists. In conclusion, INDCA demonstrated promising anti-nociceptive effects in animal models of migraine, probably through 5-HT1A/1B medicated action.

Characteristics of 5-Hydroxytryptamine Receptors Involved in Contraction of Feline Ileal Longitudinal Smooth Muscle

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the 5HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ondansetron but was inhibited by the 5-HT1 receptor antagonist methysergide and 5-HT4 receptor antagonist GR113808. These results indicate that 5-HT1 and 5-HT4 receptors may mediate the contraction of the 5-HT-induced response and 5-HT2 and 5-HT3 receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.

Interaction of 5-HT2 and 5-HT3 receptor subtype in 5-HT-induced nociceptive responses in peripheral primary sensory nerve ending / 中国应用生理学杂志

<p><b>AIM</b>To study the correlation between 5-HT-induced pain response and the contribution by individual 5-HTR subtypes including 5-HT1R, 5-HT2R and 5-HT3R at the level of peripheral primary afferent.</p><p><b>METHODS</b>The experiments were done on acutely isolated trigeminal ganglion (TG) neurons using whole-cell patch clamp technique and the nociceptive effect was observed on behavior experiments by intraplantar injection of test drugs.</p><p><b>RESULTS</b>The majority of cells examined responded to 5-HT in a manner of concentration dependence (10(-6) - 10(-3) mol/) (61.4%, 54/88) and with a fast activating and rapid desensitizing inward current (I(5-HT)), which was thought to be mediated by the activation of 5-HT3R, since it could be blocked by 5-HT3R antagonist ICS 205930 and mimicked by 5-HT3R agonist 2-methyl-5-HT. It was found that I(5-HT) was potentiated by 5-HT2R agonist alpha-methyl-5-HT markedly, while 5-HT1R agonist R-(+)-UH 301 did not. In behavioral experiment performed on conscious rats, intraplantar injection of 5-HT(10(-5), 10(-4) and 10(-3) mol/L) induced an increment of cumulative lifting time first 20 min in a manner of concentration dependence. By dissociating 5-HTR subtypes using their corresponding antagonists (ICS and CYP) the potency order of hindpaw lifting time was identified as follows: 5-HT > 5-HT + ICS > 5-HT + CYP.</p><p><b>CONCLUSION</b>The results suggest that in 5-HT-induced nociceptive response at the primary sensory level 5-HT3R may play a role of initiation, but 5-HT2R mediates maintaining and modulatory effect in the processes of nociceptive information convey.</p>

Involvement of 5-HT1A and 5-HT2 receptor in cisplatin induced emesis in dogs.

The effect of drug acting on 5-HT1A, 5-HT2 and 5-HT3 receptors were studied against cisplatin and apomorphine induced emesis in dogs. Buspirone, 5-HT1A receptor partial agonist significantly reduced the emetic episodes though it had no significant effect on emetic latency. Mianserin, 5-HT2 receptor antagonist exhibited significant reduction in emetic episodes and in latency. Buspirone prevented the apomorphine induced emesis while mianserin had no effect. The antiemetic activity of buspirone may be attributable to its agonistic activity at 5-HT1A receptor and antagonistic activity at dopamine receptors. These findings further confirm the involvement of 5-HT1A and 5-HT2 receptor in cytotoxic drug induced emesis, though the species difference in their antiemetic action can not be ruled out.

Serotonin(5-HT): can it be a cause in overactive bladder

PURPOSE: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, this study examines what drugs inhibit the serotonin-induced detrusor contractions. MATERIALS AND METHODS: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001-0.01mM) were assessed on resting tension. Electrical field stimulation (EFS), bethanechol (0.0001-0.01mM), ATP (1-3mM) or KCl(63.5-254mM)-induced contractions using application in organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS, bethanechol, ATP or KCl-induced contraction under serotonin (0.001mM) was assessed and serotonin (0.001 to 0.1mM) was cumulatively added to the organ bath following pre-incubation with propranolol, ketanserine, tropisetron, propiverine, sodium nitroprusside or doxazocin. RESULTS: There are two phases to the serotonin-induced responsean initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001mM serotonin (p<0.05). There was no effect on the responses to ATP, KCl, or EFS under 0.001mM serotonin. The 5-HT2 receptor is mainly responsible for serotonin-induced contractions of the detrusor (p<0.05), while the 5-HT1 receptor is partially responsible. Doxazocin and propiverine each significantly suppressed the responses to serotonin, while sodium nitroprusside and tropisetron each had no effect (p<0.05). CONCLUSIONS: Because the 5-HT2 antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT2 antagonist seems to improve lower urinary tract symptoms.

Involvement of dopamine D2 and 5-HT1A receptors in roxindole-induced antinociception.

Roxindole, a DA D2 receptor agonist (2-16 mg/kg) produced dose-dependent increase in percentage antinociception. The effect which was blocked by DA D2 antagonist (-)sulpiride (50 mg/kg) and 5-HT1A receptor antagonist (-) pindolol (5 mg/kg). Roxindole (4 and 8 mg/kg) reversed both naloxone (20 mg/kg)-induced hyperalgesia and reserpine (2 mg/kg)-induced hyperalgesia. This reversal was sensitive to blockade by both (-)sulpiride (50 mg/kg) and (-) pindolol (5 mg/kg). The present study suggests that roxindole-induced antinociception is mediated by postsynaptic DA D2 and 5-HT1A receptors.

Studies on the Mechanism of Renal Action of Centrally-administered TFMPP in Rabbits / 대한신장학회잡지

It has been known that central tryptaminergic system is closely related with the regulation of renal function, and that central 5-HT1 receptors mediate diuresis and natriuresis, whereas central 5-HT2 and 5-HT3 receptors mediate antidiuresis and antinatriuresis. Among many subtypes of 5-HT1 receptors, central 5-HT1A subtype has been suggested to exert diuretic and natriuretic effets. Further, it was recently observed that TFMPP, 5-HT1B agonist, elicited profound diuresis and natriuresis when administered intracerebroventricularly(icv). Present study is therefore undertaken to delineate the mechanism involved in the natriuresis and diuresis induced by icv TFMPP, employing the denervated and vagotomized rabbits. The influence of icv TFMPP on the plasma level of ANP was also observed. TFMPP 250 microgram/kg icv produced marked diuresis and natriuresis. Renal hemodynamics showed significant increase only in the first 10-min period after administration and thereafter tended to recover. However, natriuretic action lasted even after the increased renal hemodynamics returned to the control level, suggesting the decreased Na reabsorption in the tubules by humoral natriuretic factors. Systemic blood pressure transiently increased. In rabbits in which one kidney is denervated, with the contralateral intact as the control kidney, the denervated kidney also responded with natriuresis and diuresis like that of the normal rabbit. The contralateral kidney responded with typical diuretic and natriuretic effects, along with the marked increased of renal hemodynamics. The plasma ANP, one of humoral natriuretic factors, increased after administration of icv TFMPP, peaking at about 15min. In bilaterally vagotomized rabbits, the natriuretic and diuretic effects produced by icv TFMPP were greater than that of the normal rabbits. These observations suggest that the natriuresis and diuresis elicited by icv TFMPP result from the inhibition of tubular Na reabsorption mainly through mediation of ANP. It has been also suggested that vagus nerve might exert inhibitory influence on the diuretic action of icv TFMPP, because the renal effects was augmented in the vagotomized rabbits.