Oxytocin and oxytocin-receptor mRNA expression in the human gastrointestinal tract: a polymerase chain reaction study

Monstein, Hans‐Jürg; Grahn, Niclas; Truedsson, Mikael; Ohlsson, Bodil

doi:10.1016/j.regpep.2003.12.017

Cited by 80 publications

(98 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although it is reported that OTR mRNA exists on GI tissue in humans (15), according to our knowledge, this was the first time that OTR was found to be located in colon. We found that, in female rats, OTR was expressed in myenteric plexus.…”

mentioning

confidence: 66%

“…Systemic administration of atosiban, the antagonist of OT receptor (OTR), inhibited the spontaneous contraction of gallbladder in rabbits (12) and gastric emptying in humans (16). It has been well established that mRNA for OT and its receptor can be found throughout the human GI tract (15), but the cell types that express OTR were undetectable in human gut by indirect immunofluorescence (19).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Estradiol upregulates the expression of oxytocin receptor in colon in rats

Feng

Qin²,

Wang³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

The study was designed to investigate the effect of estradiol on the excitatory effect of oxytocin (OT) on colon motility. Female Wistar rats were used, and some of them were ovariectomized (OVX) and treated with vehicle or estradiol (E2). A plastic balloon made of condom was inserted into colon to monitor the change of colonic pressure in vivo. Longitudinal muscle strips of distal colon were prepared to monitor the spontaneous contraction of colon in vitro. Expression of OT receptor (OTR) was investigated by Western blot analysis. Expression of OTR mRNA was detected by RT-PCR. Immunohistochemistry was used to locate OTR. In OVX rats, pretreatment of E2 (4 -100 g/kg sc) dose-dependently increased the excitatory effect of OT on colon motility both in vivo and in vitro and increased the expression of OTR and OTR mRNA in colon. Systemic administration of OT excited the colon motility in vivo in rats at perioda of proestrus and estrus but did not influence it at diestrus period, when the concentration of plasma E2 was lowest in the estrous cycle. Pretreatment of atosiban, the specific OTR antagonist, and TTX, the blocker of voltage-dependent sodium channel on nerve fiber, attenuated the excitatory effect of OT on colon motility. OTR was located in myenteric plexus of colon. These results suggested that E2 increased the excitatory effect of OT on colon motility by upregulating the expression of OTR in myenteric plexus.colon; motility OXYTOCIN (OT) has been traditionally regarded as a hormone that is involved in parturition and milk ejection. In recent years, more evidence has indicated that OT may play a role in regulation of the gastrointestinal (GI) functions such as motility, sensation (13, 18), and immune response to inflammation (4, 10). Exogenous OT influences the GI motility, although the reports are diverse because of the differences of species, methods, and area of the gut (18, 24). It has been suggested that the effect of OT on GI motility might be physiological. OT is released in response to a fatty meal in women (16). Systemic administration of atosiban, the antagonist of OT receptor (OTR), inhibited the spontaneous contraction of gallbladder in rabbits (12) and gastric emptying in humans (16). It has been well established that mRNA for OT and its receptor can be found throughout the human GI tract (15), but the cell types that express OTR were undetectable in human gut by indirect immunofluorescence (19).In women, colonic dysmotility is very common, and bowel function changes during the reproductive cycle. Although the fluctuation of steroid hormones, especially estradiol (E 2 ) and progesterone, were believed to be the major reason, the mechanism has not been clearly illustrated. Steroid hormones regulate the activity of OTR via both genomic and nongenomic pathways (26). E 2 induced the mRNA expression of the OTR and increased the OTR density on the membranes of the uterine smooth muscle and central nervous system (8, 21). The recent study of our group also indicated that the pretreatment of E 2 increas...

show abstract

mentioning

confidence: 66%

mentioning

confidence: 99%

Estradiol upregulates the expression of oxytocin receptor in colon in rats

Feng

Qin²,

Wang³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Previous studies have suggested that the effects of oxytocin on GI motility are species dependent and vary in responses when applied to human, guinea pig, rat etc. For example, oxytocin accelerates 9,10 and oxytocin receptor antagonists delay gastric emptying in humans, 1 but oxytocin delays gastric emptying in rats. 5 The motility in the stomach, ileum and caecum was inhibited, while the motility in the colon was stimulated, in several animal species.…”

Section: Discussionmentioning

confidence: 99%

“…Oxytocin is secreted into the blood endogenously in response to after a fatty meal, and cholecystokinin (CCK) release in women. 1,2 Intravenous infusion of oxytocin leads to increased colonic peristalsis, and to accelerated gastric emptying of a meal in healthy subjects, 3 whereas an oxytocin receptor antagonist delays the gastric emptying. 4 In contrast, gastric motility is inhibited in dogs and rats.…”

Section: Introductionmentioning

confidence: 99%

“…It has recently been shown that mRNA for oxytocin and its receptor are expressed throughout the human GI tract. 1 On the other hand, metformin (1.1 dimethylbiguanide hydrochloride)belongs to the biguanide class of antidiabetic drugs that are guanidine derivatives. More recent studies have shown that metformin delays the intestinal absorption of glucose, which occurs more distally, and stimulates utilization of intestinal glucose, particularly anaerobic metabolism, which contributes to a reduction of glucose uptake in both animals and humans.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of the effect of Metformin on the inhibitory effect of oxytocin on Potassium chloride stimulated goat ileum

Anand

Vora

Tyagi

2014

Int J Basic Clin Pharmacol

View full text Add to dashboard Cite

Oxytocin Verbindungen zur oralen Behandlung von Bauchschmerzen

Kremsmayr,

Schober,

Kaltenböck

et al. 2024

Angewandte Chemie

View full text Add to dashboard Cite

Abdominal pain presents an onerous reality for millions of people affected by gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The oxytocin receptor (OTR) has emerged as a new analgesic drug target with OTR expression upregulated on colon‐innervating nociceptors in chronic visceral hypersensitivity states, accessible via luminal delivery. However, the low gastrointestinal stability of OTR’s endogenous peptide ligand oxytocin (OT) is a bottleneck for therapeutic development. Here, we report the development of potent and fully gut‐stable OT analogues, laying the foundation for a new area of oral gut‐specific peptide therapeutics. Ligand optimisation guided by structure‐gut‐stability‐activity relationships yielded highly stable analogues (t1/2 >24 h, compared to t1/2 <10 min of OT in intestinal fluid) equipotent to OT (~3 nM) and with enhanced OTR selectivity. Intra‐colonic administration of the lead ligand significantly reduced colonic mechanical hypersensitivity in a concentration‐dependent manner in a mouse model of chronic abdominal pain. Moreover, oral administration of the lead ligand also displayed significant analgesia in this abdominal pain mouse model. The generated ligands and employed strategies could pave the way to a new class of oral gut‐specific peptides to study and combat chronic gastrointestinal disorders, an area with substantial unmet medical needs.

show abstract

Oxytocin and oxytocin-receptor mRNA expression in the human gastrointestinal tract: a polymerase chain reaction study

Cited by 80 publications

References 32 publications

Estradiol upregulates the expression of oxytocin receptor in colon in rats

Estradiol upregulates the expression of oxytocin receptor in colon in rats

Evaluation of the effect of Metformin on the inhibitory effect of oxytocin on Potassium chloride stimulated goat ileum

Oxytocin Verbindungen zur oralen Behandlung von Bauchschmerzen

Contact Info

Product

Resources

About