BIOMAT Database Logo BIOMAT Database Logo

Pharmacological characterization of 5-HT4 receptors mediating relaxation of canine isolated rectum circular smooth muscle. 1999

N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium.

This study aimed to characterize for the first time in vitro 5-HT4 receptors in the canine gastrointestinal tract. For this purpose, we used circular muscle strips of the canine isolated rectum. In the presence of methysergide (60 microM), 5-HT induced relaxation of methacholine (1 microM)-precontracted muscle strips, yielding a monophasic sigmoidal concentration-relaxation curve (pEC50 7.2+/-0.07). Tetrodotoxin (0.3 microM) did not affect the curve to 5-HT, suggesting the inhibitory 5-HT receptor is located on the smooth muscle. Granisetron (0.3 microM) did also not affect the curve to 5-HT, which excludes the 5-HT3 receptor mediating the relaxation to 5-HT. The presence of methysergide rules out the involvement of 5-HT1, 5-HT2 or 5-HT7 receptors. 5-HT, the selective 5-HT4 receptor agonists R076186, prucalopride (R093877) and SDZ HTF-919 and the 5-HT4 receptor agonists cisapride and 5-MeOT relaxed the muscle strips with a rank order of potency R076186 = 5-HT > cisapride > prucalopride > or = SDZ HTF-919 > 5-MeOT. The selective 5-HT4 receptor antagonists GR 125487, RS 39604 and GR 113808 competitively antagonized the relaxations to 5-HT, yielding pK(B) estimates of 9.7, 7.9 and 9.1, respectively. The selective 5-HT4 receptor antagonist SB 204070 shifted the curve to 5-HT rightward and depressed the maximal response (apparent pA2 10.6). GR 113808 (10 nM) produced a parallel rightward shift of the curve to the selective 5-HT4 receptor agonists R076186 (pA2 8.8). It is concluded that 5-HT induces relaxation of the canine rectum circular muscle through stimulation of a single population of smooth muscle 5-HT4 receptors. For the first time, a nonhuman species was shown to exhibit relaxant 5-HT4 receptors in the large intestine.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D008297 Male Males
D008735 5-Methoxytryptamine Serotonin derivative proposed as potentiator for hypnotics and sedatives. Meksamine,Methoxytryptamine,Mexamine,5 Methoxytryptamine
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009130 Muscle, Smooth Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed) Muscle, Involuntary,Smooth Muscle,Involuntary Muscle,Involuntary Muscles,Muscles, Involuntary,Muscles, Smooth,Smooth Muscles
D011985 Receptors, Serotonin Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. 5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D012007 Rectum The distal segment of the LARGE INTESTINE, between the SIGMOID COLON and the ANAL CANAL. Rectums
D003106 Colon The segment of LARGE INTESTINE between the CECUM and the RECTUM. It includes the ASCENDING COLON; the TRANSVERSE COLON; the DESCENDING COLON; and the SIGMOID COLON. Appendix Epiploica,Taenia Coli,Omental Appendices,Omental Appendix,Appendices, Omental,Appendix, Omental
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response

Related Publications

N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Pharmacological characterization of the 5-HT receptors mediating contraction and relaxation of canine isolated proximal stomach smooth muscle.
May 2002, British journal of pharmacology,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Pharmacological characterization of beta-adrenoceptor subtypes mediating relaxation in porcine isolated ureteral smooth muscle.
September 2004, The Journal of urology,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Pharmacological evidence for the 5-HT7 receptor mediating smooth muscle relaxation in canine cerebral arteries.
June 1999, British journal of pharmacology,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Characterization of 5-hydroxytryptamine receptors mediating circular smooth muscle contraction in the human umbilical artery.
January 1999, Gynecologic and obstetric investigation,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Pharmacological studies of tachykinin receptors mediating contraction of isolated airway smooth muscle.
January 1991, Annals of the New York Academy of Sciences,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
An analysis of 5-hydroxytryptamine receptors mediating contraction of isolated smooth muscle.
December 1984, Neuropharmacology,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Pharmacological characterization of bradykinin receptors in canine cultured tracheal smooth muscle cells.
January 1995, British journal of pharmacology,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Characterization of opioid receptors on isolated canine gallbladder smooth muscle cells.
January 1988, Life sciences,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Pharmacological characterization of the 5-hydroxytryptamine receptor mediating relaxation in the rat isolated ileum.
September 1996, British journal of pharmacology,
N H Prins, and J F Van Haselen, and R A Lefebvre, and M R Briejer, and L M Akkermans, and J A Schuurkes
Smooth muscle 5-HT2A receptors mediating contraction of porcine isolated proximal stomach strips.
December 2002, British journal of pharmacology,
Copied contents to your clipboard!