WHICH TYPE OF 5-HYDROXYTRYPTAMINE RECEPTOR MEDIATES RELAXATION OF THELONGITUDINAL MUSCLE OF GUINEA-PIG PROXIMAL COLON IN-VITRO

Concentration-dependent 5-hydroxytryptamine (5-HT) relaxations of guin ea pig proximal colon were evoked in the presence of atropine (0.2 mu M). 5-HT effect was neuronally mediated since it was blocked by tetrod otoxin (TTX) (0.5 mu M). The type of 5-HT receptor medicating the rela xations was investigated using both 5-HT agonists and antagonists. Sel ective 5-HT3 antagonists tropisetron (10, 50, 500 mM) and ondansetron (1 mu M) shifted the concentration-response curves for 5-HT to the rig ht. Another 5-HT3 antagonist MDL 72222 (0.5 mu M), 5-HT1/5-HT2 antagon ists methiothepin (0.1 mu M) and metergoline (0.1 mu M), 5-HT1A,B anta gonist propranolol (1 mu M) and 5-HT1B antagonist isamoltane (10 nM) w ere ineffective. Specific agonist of 5-HT3 receptors 2-methyl-5-hydrox ytryptamine (2-methyl-5-HT) and agonist of 5-HT1 receptors 5-carboxami dotryptaime (5-CT) also relaxed the preparation, although the relaxati on was not 5-HT relaxation. Neither was it neurogenic because it persi sted in the presence of TTX (0.5 mu M). The concentration-response cur ve for 2-methyl-5-HT was not affected by ondansetron (1 mu M) or tropi setron (0.5 mu M), but it was shifted to the right in the presence of 5-HT1/5-HT2 receptor antagonists methiothepin (0.1 mu M) and metergoli ne (0.1 mu M) and in the presence of 5-HT1Da/5-HT2A receptor antagonis t ketanserin (1 mu M). Methiothepin (0.1 mu M) also inhibited the rela xations evoked in the presence of 5-CT. Specific agonist of 5-HT4 rece ptors 5-methoxytryptamine did not exert any effect on the preparation. It is suggested that there are two different mechanisms of relaxation in the guinea pig proximal colon. One is neurogenic and involves the activation of 5-HT3 receptors located on inhibitory neurons to the mus cle; the other is myogenic and might be mediated via yet unclassified 5-HT receptors located on the muscle.