NOVEL 5-HT2-LIKE RECEPTOR MEDIATES NEUROGENIC RELAXATION OF THE GUINEA-PIG PROXIMAL COLON

The aim of the current investigation was to characterize the 5-HT rece ptors that mediate neurogenic relaxation of the guinea-pig proximal co lon. After blockade of 5-HT2A, 5-HT3 and 5-HT4 receptor-mediated contr actions, 5-hydroxytryptamine (5-HT) induced relaxations yielding a bip hasic concentration-response curve. Other tryptamines were also agonis ts with the following rank order of potency: 5-HT > 5-carboxamidotrypt amine = 5-methoxytryptamine greater than or equal to alpha-methyl-5-HT (partial agonist) > tryptamine (partial agonist). 5-Hydroxytryptophan , 2-methyl-5-HT and N-methyltryptamine were virtually inactive as agon ists. The curve to 5-HT was not affected by pargyline, citalopram, phe ntolamine, or by the 5-HT4 receptor antagonists 2-methoxy-4-amino-5-ch loro-benzoic acid 2-(diethylamino)ethyl ester (SDZ 205-557) and (1-but yl-4-piperidinylmethyl)-8-amino-7- chloro-1,4-benzodioxan-5-carboxylat e (SE 204070). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), ho xy-3[1,2,3,6-tetrahydroxypyridin-4-yl]-1H-indole (RU 24969), 2-(2,6-di methoxyphenoxyethyl)aminomethyl- 1,4-benzodioxane (WE 4101), 1-(3-chlo rophenyl)piperazine (mCPP), 1-(m-trifluoromethylphenyl)-piperazine (TF MPP), flesinoxan, sumatriptan and 6-chloro-2-(piperazinyl)-pyrazine (M K212) were inactive as 5-HT receptor agonists. The first phase of the curve to 5-HT was inhibited by: metergoline (pA(2) = 8.8 +/- 0.3, agai nst 5-methoxytryptamine 9.3 +/- 0.3), methysergide (non-surmountable), methiothepin (nonsurmountable), spiroxatrine (non-surmountable), MK21 2 (non-surmountable), mesulergine (7.8 +/- 0.3), mCPP (7.1 +/- 0.1), m ianserin (7.0 + 0.4), ritanserin (8.9 +/- 0.2), rauwolscine (7.0 +/- 0 .2), yohimbine (6.2 +/- 0.2), 1-(1-naphthyl)-piperazine (7.7 +/- 0.2) and RU 24969 (6.4 +/- 0.1), but not by methoxyphenyl)-4-[4-(2-phthalim idobtyl]-piperazine (NAN-190), spiperone, sumatriptan, 8-OH-DPAT and f lesinoxan. It is suggested that the 5-HT receptor under study could be considered an unknown 5-HT2-like receptor.