Characterization of the receptors involved in the 5-HT-induced excitation of canine antral longitudinal muscle.
1. We aimed to characterize the 5-HT receptors involved in the 5-HT-induced effect on electrically induced contractions of dog antrum longitudinal muscle in vitro. 2. In the presence of L-NOARG (0.1 mM), electrical field stimulation (EFS) induced atropine- and tetrodotoxin-sensitive contractions. Tetrodotoxin or atropine left any agonist tested ineffective. These EFS-induced contractions were on average enhanced by 5-HT (0.3 microM), however, pronounced variation in the response to 5-HT was observed. There were non-significant trends of the selective 5-HT3 receptor antagonist granisetron (1 microM), and methysergide (1 microM; preventing interactions of 5-HT with 5-HT1, 5-HT2, 5-ht5, 5-HT6 and 5-HT7 receptors) to increase the response to 5-HT. The selective 5-HT4 receptor antagonist GR 113808 (0.1 microM) displayed a non-significant trend to inhibit the 5-HT-induced increase. 3. Combination experiments with methysergide (1 microM), granisetron (1 microM) and GR 113808 (0.1 microM) revealed that the 5-HT (0.3 microM)-induced response consisted of (1) an excitatory component blocked by GR 113808, (2) excitatory and inhibitory components both blocked by methysergide. 4. The selective 5-HT4 receptor agonist prucalopride (0.3 microM) increased EFS-induced contractions, an effect prevented by GR 113808 (0.1 microM). 5. The increase of EFS-induced contractions by the preferential 5-HT2 receptor agonist alpha-Me-5-HT (0.3 microM) was antagonized by 5-HT2B receptor antagonists. 6. The 5-HT1/5-HT7 receptor agonist 5-carboxamidotryptamine (5-CT; 0.3 microM) inhibited EFS-induced contractions. This was prevented by methysergide (1 microM), the 5-HT7 receptor antagonist mesulergine (0.3 microM) and the selective 5-HT7 receptor antagonist SB-269970 (0.3 microM). 7. In the presence of GR 113808 (0.1 microM), alpha-Me-5-HT (1 microM) increased EFS-induced contractions. The 5-HT (0.3 microM)-induced inhibition of the stimulation by alpha-Me-5-HT was prevented by SB-269970 (0.3 microM). 8. In conclusion, dog antral longitudinal muscle is endowed with (1) excitatory neuronal 5-HT4 receptors and 5-HT2B receptors and (2) inhibitory smooth muscle 5-HT7 receptors.
Prins
N H
NH
Department of Gastrointestinal Pharmacology, Janssen Research Foundation, Beerse, Belgium. kprins@janbe.jnj.com
Akkermans
L M
LM
Lefebvre
R A
RA
Schuurkes
J A
JA
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D017829:Granisetron / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology*; D011706:Pyloric Antrum / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
D001285:Atropine; D017829:Granisetron; D007211:Indoles; D008784:Methysergide; D019335:Nitroarginine; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013779:Tetrodotoxin; D014363:Tryptamines; C082871:GR 113808