Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 5-HT4 receptor is a member of the seven transmembrane spanning G-protein-coupled family of receptors. The receptor is positively coupled to adenylate cyclase and exists in two isoforms (5-HT4S and 5-HT4L) that differ in the length and sequence of their carboxy termini. 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. The receptor is widely distributed in the central nervous system and peripheral tissues. In the periphery, the receptor plays an important role in the function of several organ responses including the alimentary tract, urinary bladder, heart and adrenal gland. In the alimentary tract, stimulation of 5-HT4 receptors has a pronounced effect on smooth muscle tone, mucosal electrolyte secretion, and the peristaltic reflex. In the urinary bladder, activation of 5-HT4 receptors modulates cholinergic/purinergic transmission. In the heart, stimulation of atrial 5-HT4 receptors produces positive inotropy and tachycardia that can precipitate arrhythmias. In the adrenal gland, agonism of 5-HT4 receptors stimulates release of cortisol, corticosterone, and aldosterone. Since its discovery in 1988, significant advances have been made in our understanding of the physiology and pharmacology of the 5-HT4 receptor. These advances have led to the development of several selective 5-HT4 receptor agonists and antagonists that may have therapeutic utility in the treatment of peripheral disorders such as irritable bowel syndrome, gastroparesis, urinary incontinence and cardiac arrhythmias.
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PMID:Peripheral 5-HT4 receptors. 890 10

Elevated amygdala activity and increased responsiveness of the hypothalamic-pituitary-adrenal axis have been observed in irritable bowel syndrome (IBS) patients. Recently, we demonstrated that corticosterone (Cort) placed on the amygdala induced anxiety-like behavior coupled with decreased thresholds for visceral and somatic pain in rats. Moreover, these studies suggested that the effects of Cort were dependent on both the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR); however, the specific contributions of these receptors to the interaction between corticosteroids and the amygdala are still unclear. In the present study, we sought to define the distinct roles of amygdaloid GR and MR in anxiety-like behavior, visceral sensitivity, and somatic sensitivity through selective pharmacological activation. Male Fischer 344 rats received bilateral implants on the dorsal margin of the central amygdala containing the GR agonist dexamethasone (Dex), the MR agonist aldosterone (Aldo), or cholesterol as a control. Our results showed that GR or MR activation significantly reduced open arm exploration on the elevated plus maze, a measure of anxiety-like behavior. Aldo increased the number of abdominal muscle contractions in response to all levels of colorectal distension (CRD). In contrast, Dex only increased visceral sensitivity at noxious levels of CRD. Furthermore, GR but not MR activation reduced somatic pain thresholds measured by the mechanical force required to elicit hindlimb withdrawal. In summary, GR and MR mediated-mechanisms induce anxiety and visceral hypersensitivity, whereas somatic sensitivity involves only GR, suggesting that corticosteroids may enhance visceral and somatic sensation via divergent processes originating in the amygdala and involving specific steroid receptor mechanisms.
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PMID:Divergent effects of amygdala glucocorticoid and mineralocorticoid receptors in the regulation of visceral and somatic pain. 1987 99