Identification and characterization of the 5-HT4 receptor in the intestinal tract and striatum of the guinea pig

A comparison of the pharmacological properties of guinea‐pig and human recombinant 5‐HT4 receptors

“…The pharmacological and functional properties of the guinea‐pig recombinant 5‐HT 4 receptor, in general, were very similar to those of guinea‐pig native receptors. As expected, the pK i values for a range of 5‐HT 4 receptor selective agonists and antagonists at the recombinant receptor were similar to those at native 5‐HT 4 receptors in guinea‐pig striatal (present study; Uchiyama‐Tsuyuki et al ., 1996 ) and ileal ( Uchiyama‐Tsuyuki et al ., 1996 ) membrane preparations.…”

“…The corresponding density of [ 3 H]GR113808 binding sites in the ileum and proximal colon was ∼30 fmol mg −1 protein. This is consistent with values of 45 ( Yoshikawa et al ., 1998 ) or 12 ( Uchiyama‐Tsuyuki et al ., 1996 ) fmol mg −1 protein, obtained previously for [ 3 H]GR113808 binding to guinea‐pig ileum. In humans, there has been no direct measurement of 5‐HT 4 receptor densities in the digestive tract.…”

“… Leung et al ., 1996 ). It should be noted, however, that there is an excellent correlation between the binding affinities for a range of agonist and antagonist ligands at 5‐HT 4 receptors in striatal and ileal/colon membrane preparations ( Uchiyama‐Tsuyuki et al ., 1996 ). In addition, in the present study, the properties of the guinea‐pig 5‐HT 4 receptor were compared directly with the prevalent human 5‐HT 4(b) receptor splice variant, with which it shares ∼95% identity, as well as high similarity within the C‐terminus.…”

Small Bowel Review: Part II

“…5-HT 4 receptor stimulation increases peristaltic reflux sensitivity, and the relaxant response to 5-HT in the terminal ileum is mediated directly on the smooth muscle (209). There is specific binding of 5-HT to the 5-HT 4 receptors in longitudinal muscle and myenteric plexus of the guinea pig, with a larger number of binding sites in the proximal than in the distal intestine (210). In rat jejunum, 5-HT produces a biphasic concentration-effect curve, which is mediated by a putative 5-HT 7 (first phase) and 5-HT 3 (second phase) receptor mechanism (211).…”

5-HT4 Receptor Antagonists: Structure-Affinity Relationships and Ligand- Receptor Interactions

“…In addition to the CNS [28][29][30][31] and the GI system [32][33][34][35][36][37][38][39][40][41][42][43] the 5-HT 4 R has been localized in several animal and human peripheral tissues, such as the heart [44][45][46], the urinary bladder [47,48] and the adrenal gland [49,50], where they mediate a variety of responses. Thus, certain 5-HT 4 R agonists are clinically used as prokinetic agents in the treatment of GI motility disorders [51][52][53][54][55], and their possible utility in memory deficits is currently under investigation [29,[56][57][58][59][60][61][62][63][64][65][66].…”