5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine

Grider, John R.; Foxx‐Orenstein, Amy E.; Jin, Ji‐Guang

doi:10.1016/s0016-5085(98)70203-3

Cited by 330 publications

(299 citation statements)

References 20 publications

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“…However, although this receptor sub-type has been proposed to be identical to the 5-HT4 receptor (Grider et al, 1996), it is thought to be unrelated to the 5-HT4 receptor by others (Galligan et al, 1996;Gershon, 2004). Either way, both of these receptor types are important because each has been implicated in the initiation of peristaltic reflexes (Gershon, 2004;Grider et al, 1998;Jin et al, 1999). Since the discovery of 5-HT4 receptors in 1988, significant advances have been made in our understanding of their physiology and pharmacology.…”

Section: -Ht Receptorsmentioning

confidence: 99%

“…The 5-HT4 receptor is pharmacologically defined by selective agonists such as SC 53116 and RS 67506, and selective antagonists such as GR 113808, SB 204070 and RS 39604 (Gale et al, 1994;Hegde et al, 1996). In the gastrointestinal tract, stimulation of 5-HT4 receptors has a pronounced effect on smooth muscle tone, mucosal electrolyte secretion, and on the peristaltic reflex (Costall et al, 1993;Grider et al, 1998;Hegde et al 1996;Jin et al, 1999;Kadowaki et al, 2002). SakuraiYamashita et al (1999SakuraiYamashita et al ( , 2000 have recently reported that 5-HT4 receptors are distributed in the human sigmoid colon, guinea pig distal colon and human rectum.…”

Section: -Ht Receptorsmentioning

confidence: 99%

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Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Kojima

Fujii

Katsui

et al. 2006

J. Smooth Muscle Res.

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The defecation reflex is composed of rectal distension-evoked rectal (R-R) reflex contractions and synchronous internal anal sphincter (R-IAS) reflex relaxations in guinea pigs. These R-R and R-IAS reflexes are controlled via extrinsic sacral excitatory nerve pathway (pelvic nerves), lumbar inhibitory nerve pathways (colonic nerves) and by intrinsic cholinergic excitatory and nitrergic inhibitory nerve pathways. The effect of mosapride (a prokinetic benzamide) on the intrinsic reflexes, mediated via enteric 5-HT4 receptors, was evaluated by measuring the mechanical activity of the rectum and IAS in anesthetized guinea pigs using an intrinsic R-R and R-IAS reflex model resulting from chronic (two to nine days) lumbosacral denervation (PITH). In this model, the myenteric plexus remains undamaged and the distribution of myenteric and intramuscular interstitial cells of Cajal is unchanged. Although R-R and R-IAS reflex patterns markedly changed, the reflex indices (reflex pressure or force curve-time integral) of both the R-R contractions and the synchronous R-IAS relaxations were unchanged. The frequency of the spontaneous R and IAS motility was also unchanged. Mosapride (0.1-1.0 mg/kg) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indices (maximum: 2.76) from that of the control (1.0) 6-9 days following chronic PITH. The dose-response curve was similar to that in the intact guinea pig, and had shifted to the left from that in the guinea pig after acute PITH. A specific 5-HT4 receptor antagonist, GR 113808 (1.0 mg/kg), decreased both reflex indices by approximately 50% and antagonized the effect of mosapride 1.0 mg/kg. This was quite different from the result in the intact guinea pig where GR 113808 (1.0 mg/kg) did not affect either of the reflex indices. The present results indicate that mosapride enhanced the intrinsic R-R and R-IAS reflexes and functionally compensated for the deprivation of extrinsic innervation. The actions of mosapride were mediated through endogenously active, intrinsic 5-HT4 receptors which may be post-synaptically located in the myenteric plexus of the anorectum.

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Section: -Ht Receptorsmentioning

confidence: 99%

Section: -Ht Receptorsmentioning

confidence: 99%

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Kojima

Fujii

Katsui

et al. 2006

J. Smooth Muscle Res.

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“…Oral administration of buspirone improves gastric accommodation [13], accelerates interdigestive gastrointestinal motility in man [14] and increases oesophageal wave amplitude and wave progression velocity and reduces the duration and extent of lower oesophageal sphincter relaxation in healthy volunteers [15], suggesting a wide regulatory effect of this receptor on gastrointestinal motility. Other 5-HT receptors were shown to be important in the regulation of intestinal motility, as 5-HT4 and 5-HT3 are the main receptors involved in gastrointestinal peristalsis [16,17].…”

Section: Discussionmentioning

confidence: 99%

Patients with headache and functional dyspepsia present meal–induced hypersensitivity of the stomach

Pucci

Miceli

et al. 2005

J Headache Pain

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IntroductionFunctional gastrointestinal disorders are frequently characterised by the presence of extra-intestinal symptoms. A survey on irritable bowel syndrome showed that gynaecological, urinary, psychological, dermatological and neurological symptoms were significantly more prevalent in patients than in controls [1]. Headache, in particular, was present in more than 30% of patients suffering from this condition. Although there is no similar evaluation for functional dyspepsia, the presence of headache also in patients suffering from this functional disorder is a common finding in day-today clinical practice. To our knowledge no data are available on the responsible pathophysiological mechanism.A new instrument recently became available, the barostat, which allows the evaluation of both tone modifications of large viscera, such as the stomach and colon, and the evaluation of visceral sensitivity, by the study of sensitivity thresholds to mechanical distention [2]. The application of this new technology to the study of the pathophysiology of functional dyspepsia has made it possible to identify several mechanisms at the basis of the onset of dyspeptic symptoms: for example, it was shown that the onset of post-prandial epigastric pain, belching and weight loss is due to gastric hypersensitivity to distention Abstract Headache is a frequent feature of functional gastrointestinal disorders but there is no data on the responsible pathophysiological mechanism. The aim of this study was to verify whether alteration of post-prandial gastric tone or sensitivity might explain this association. Fourteen patients affected by functional dyspepsia (7 migraine without aura) and 7 healthy volunteers (HV) underwent gastric tone measurement in fasting condition and after the administration of a liquid meal by barostat. Gastric volume (GV) and accommodation were calculated as difference between mean post-prandial and mean fasting volume. Mean postprandial GV increase and fasting perception and discomfort threshold (DTh) were similar among the 3 groups. DTh after meal was lower in dyspeptic headache patients than in HV and dyspeptic without headache patients. Patients with migraine and functional dyspepsia may be characterised by mealinduced hypersensitivity of the stomach.

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“…Many subtypes of 5-HT receptor distribute heterogeneously in gastrointestinal tissues, in prejunctional and postjunctional membranes and also in ICC, and each subtype of receptors has different actions (Liu et al, 2005). Gastrointestinal smooth muscle has a distribution of 5-HT4 receptors, and their activation produces a muscle relaxation in the rat oesophagus (Baxter et al, 1991), human intestine (Grider et al, 1998;Grider, 2003), human colon and rat ileum (Tuladhar et al, 1994). Activation of presynaptic 5-HT receptors enhances the release of acetylcholine (ACh) in the myenteric neurons (Kilbinger and Wolf, 1992;Pan and Galligan, 1994;Galligan et al, 2003), and facilitates peristaltic reflexes (Grider et al, 1998;Foxx-Orenstein et al, 1998;Grider, 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Gastrointestinal smooth muscle has a distribution of 5-HT4 receptors, and their activation produces a muscle relaxation in the rat oesophagus (Baxter et al, 1991), human intestine (Grider et al, 1998;Grider, 2003), human colon and rat ileum (Tuladhar et al, 1994). Activation of presynaptic 5-HT receptors enhances the release of acetylcholine (ACh) in the myenteric neurons (Kilbinger and Wolf, 1992;Pan and Galligan, 1994;Galligan et al, 2003), and facilitates peristaltic reflexes (Grider et al, 1998;Foxx-Orenstein et al, 1998;Grider, 2003). Two types of 5-HT receptor (5-HT1 and 5-HT4) distribute in the prejunctional membrane of myenteric cholinergic nerves, and activation of 5-HT4 receptors increases and that of 5-HT1 inhibits the release of ACh from nerves (Taniyama et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

Effects of 5-hydroxytryptamine on electrical responses of circular smooth muscle isolated from the guinea-pig gastric antrum

Kim

Hayase

Nakamura

et al. 2006

J. Smooth Muscle Res.

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The effects of 5-hydroxytryptamine (5-HT) on electrical responses of the membrane were investigated in circular smooth muscle isolated from the guinea-pig stomach antrum. Small segment of circular muscle tissue produced a periodical generation of slow potentials at frequency of 0.1-2 cycles min solution or in the presence of glybenclamide, suggesting that the hyperpolarization was produced by activation of ATP-sensitive K-channels. The increase in amplitude of slow potentials by 5-HT may be secondary due to hyperpolarization of the membrane. The inhibition by 5-HT of the frequency of slow potentials may be partly due to the increased release of NO, however the mechanism by which dual effects of 5-HT on the frequency of slow potentials remains unsolved.

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5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine

Cited by 330 publications

References 20 publications

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Enhancement of the intrinsic defecation reflex by mosapride, a 5-HT4 agonist, in chronically lumbosacral denervated guinea pigs

Patients with headache and functional dyspepsia present meal–induced hypersensitivity of the stomach

Effects of 5-hydroxytryptamine on electrical responses of circular smooth muscle isolated from the guinea-pig gastric antrum

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