Is sulfotep a proctolin receptor antagonist?

Proctolin‐induced, dose‐dependent (10⁻⁸‐2 × 10⁻⁶ M) contraction of the isolated foregut of Schistocerca gregaria was antagonised non‐competitively by sulfotep (2 × 10⁻⁶‐10⁻⁵ M). A higher dose of sulfotep (5 × 10⁻⁵ M) caused restoration of the proctolin dose‐response curve to its control value. Neostigmine (10⁻⁵ M) caused non‐competitive inhibition of proctolininduced tissue contraction. Increasing the dose of neostigmine to 10⁻⁴ M restored the proctolin response to control values. Sulfotep (10⁻⁵ M) and neostigmine (10⁻⁴ M) caused inhibition of acetylcholinesterase (AChE) activity in tissue homogenates obtained from guts pretreated with either drug for 20 min. The stimulatory effect of sulfotep (5 × 10⁻⁵ M) on proctolin‐induced gut contraction was abolished by pretreatment of tissues with atropine (10⁻⁶ M). Under these conditions, 5 × 10⁻⁵ M sulfotep caused further antagonism of the action of proctolin. The results suggest that sulfotep is a proctolin receptor antagonist in the locust foregut. However, higher concentrations inhibit tissue AChE activity, thereby allowing endogenous acetylcholine to activate muscarinic receptors. This leads to enhanced tissue contractility which masks the antagonistic effect of sulfotep on proctolin‐induced contraction.