Investigation of the 5-hydroxytryptamine receptor mediating the "transient" short-circuit current response in...

5-Hydroxytryptamine (5-HT) stimulated an increase in short-circuit current (ISC) in guinea-pig isolated ileal mucosa over a wide concentration range (0.1 nM-0.1 mM). The concentration-response relationship was biphasic, consisting of a high potency phase (0.1 nM-1 microM) and a low potency phase (3-10 microM). Stimulation of ISC observed at the high potency phase tended to be sustained while responses at the low potency phase (3-10 microM) contained two components, an initial "transient" response followed by a "maintained" response. Both the high potency phase (maximum stimulation approximately 30 microA cm-2) and the low potency phase (maximum stimulation approximately 80 microA cm-2) 5-HT response were antagonized by tetrodotoxin (TTX, 0.3 microM) and atropine (1 microM). However, another low potency (3 microM-0.1 mM, maximum stimulation approximately 30 microA cm-2) component of the 5-HT response was revealed in the presence of TTX or atropine. In the presence of methysergide (1 microM), the concentration-response relationship of 5-HT was still biphasic and tropisetron (0.1 and 10 microM) antagonized both phases of the 5-HT response. In the presence of methysergide, the high potency phase 5-HT response was mimicked by 5-methoxytryptamine (5-MeOT) and the selective 5-HT4 agonist SC-53116 but not by BIMU 8. The potent 5-HT4 antagonist GR 113808 antagonized the response to 5-MeOT in a surmountable manner with an affinity estimate of 9.6 +/- 0.3 (n = 4).(ABSTRACT TRUNCATED AT 250 WORDS)