Pharmacological characterisation of 5-hydroxytryptamine-induced contractile effects in the isolated gut of the lepidopteran caterpillar Spodoptera frugiperda

The indolealkylamine 5-hydroxytryptamine (5-HT, 0.1 nM–1 μM) caused dose-dependent increases in the number of contractions observed in guts isolated from the caterpillar Spodoptera frugiperda. Of the 5-HT analogues tested for agonist action, 2-methyl-5-HT (0.1–10 μM) was a full agonist with reduced potency while α-methyl-5-HT (0.1–100 μM), 5-carboxamidotryptamine (0.1–100 μM), 5-methoxytryptamine (5-MeOT) (10 nM–10 μM), and tryptamine (1–100 μM) were partial agonists. Incubation of isolated guts with proven mammalian 5-HT receptor antagonists showed that cyproheptadine (10 nM–1 μM), MDL 72222 (1–10 μM), tropisetron (1–10 μM) and 5-benzoyloxygramine (1–10 μM) were potent non-competitive antagonists of 5-HT-induced tissue contraction. In comparison, ketanserin (0.1–1 μM) was a competitive antagonist. The mammalian selective serotonin reuptake inhibitors, clomipramine (10 nM–10 μM) and fluoxetine (10 nM–10 μM) also caused non-competitive inhibition of 5-HT-induced contraction while fluvoxamine (10 nM–10 μM) was a weak competitive antagonist. Low doses of clomipramine (0.1 μM) caused potentiation of 5-HT-induced gut contraction thereby suggesting the presence of 5-HT reuptake systems in this tissue. The contractile effects of 5-HT were inhibited by verapamil, Li+ and H7 and potentiated by theophylline thereby indicating that L-type Ca2+ channels, phosphatidylinositol second messengers and cAMP, respectively, are involved in 5-HT-induced tissue contraction. The 5-HT receptors mediating contractility in the gut of S. frugiperda have properties in common with mammalian 5-HT2 and Drosophila 5-HTdro2A/2B receptors. In addition, these data suggest that the tissue also contains receptors that are similar to mammalian 5-ht6 and 5-HT7 as well as Drosophiladro1 receptors. However, the primary amino acid sequence of these lepidopteran 5-HT receptors will have to be elucidated before full comparisons can be made.