Pharmacological characterization of 5-hydroxytryptamine receptors in the canine terminal ileum and ileocolonic junction.
The effects of 5-hydroxytryptamine (5-HT), the 5-HT1-like receptor agonist 5-carboxamidotryptamine and the 5-HT3 receptor agonist 2-methyl-5-hydroxytryptamine were studied on circular muscle strips of the canine terminal ileum and ileocolonic junction. Serial administration of 5-HT or of 5-carboxamidotryptamine induced slow tonic contractions that at higher concentrations of 5-HT (10(-4)-3 x 10(-4] were preceded by an initial relaxation and a fast phasic contraction. The concentration-response curves to both agonists were competitively shifted to the right by the mixed 5-HT1/5-HT2 receptor antagonist methysergide. The initial relaxation and fast phasic contraction were inhibited by the 5-HT3 receptor antagonist ICS 205-930 and tetrodotoxin. Atropine blocked the fast phasic contraction, but enhanced the relaxation. During acetylcholine-induced contractions, 5-HT and 2-methyl-5-hydroxytryptamine (greater than or equal to 10(-5) M), but not 5-carboxamidotryptamine, evoked relaxations that were blocked by ICS 205-930 and tetrodotoxin, but not by adrenoceptor antagonists. Thus, in the canine terminal ileum and ileocolonic junction, 5-HT stimulates neuronal 5-HT3 receptors and excitatory 5-HT1-like receptors located on smooth muscle. Stimulation of the 5-HT3 receptors results in an acetylcholine-mediated contraction and a relaxation mediated by an as yet unknown nonadrenergic noncholinergic neurotransmitter.
Boeckxstaens
G E
GE
Division of Gastroenterology, Faculty of Medicine, University of Antwerp (UIA), Antwerpen-Wilrijk, Belgium.
Pelckmans
P A
PA
Rampart
M
M
Bogers
J J
JJ
Verbeuren
T J
TJ
Herman
A G
AG
Van Maercke
Y M
YM
D000818:Animals; D003106:Colon; D046508:Culture Techniques; D004285:Dogs; D005260:Female; D007082:Ileum; D007211:Indoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009469:Neuromuscular Junction / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077526:Tropisetron
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000077526:Tropisetron; C047087:5-carboxamidotryptamine; D007650:Ketanserin; D008784:Methysergide