Myotropic effects of proctolin analogues, modified in position 2 of the peptide chain, on the foregut of the locust Schistocerca gregaria

Proctolin, an insect neuropeptide

“…In addition to the cockroach proctodeum [3,8,10,12], proctolin stimulates contractions of foregut of the locust S. gregaria [27,[29][30][31] and the midgut of the cockroach Diploptera punctata [32], and it is now regarded as the main neuromuscular transmitter/modulator in the gut of most insect species [8,10,12,15,32]. Further, it induces myogenic contractions of the extensor tibiae in Locusta [33], and the of coxal depressor in Periplaneta [34]; it stimulates oviduct contractility in Periplaneta [35], Leucophaea [8,36] and Locusta [37]; and it increases the rate of contraction of the hyperneural muscle in Periplaneta [38] and the dorsal longitudinal muscles of Teleogryllus oceanicus [39].…”

“…Cyclo-proctolin [67] and an analogue with the peptide bond isostere -CH 2 -O -between Tyr 2 and Leu 3 (Tyr 2 --Leu 3 ) [72] have also been synthesized. Biological studies of proctolin analogues have focused on the contraction of the hindgut muscles of the cockroach P. americana [27,54], heart-beat frequency in P. americana or T. molitor [22,50 -53], the oviduct of L. migratoria [10,24,68], and foregut contraction in S. gregaria [31,67,73]. Out of 100 proctolin analogues, 45 had an agonistic effect in selected insect species, whereas five compounds showed antagonistic properties (Tables 2 and 3).…”

“…Arg-Tyr-Leu-X 4 -Thr; X 4 = D-Pro [27] Pro(4-OMe); Thz; ihomo-Pro; Ach; Sar [74,82] Arg-Tyr-Leu-Pro-X 5 ; X 5 = D-Thr; Ser; Thr-NH 2 [27,79,83] MeThr [67] D-Val [83] Other proctolin analogues Arg-Tyr-Leu-Pro-Thr-NH 2 , [27] Tyr-Leu-Pro-Thr, Leu-Pro-Thr [79] Arg-Tyr-Leu-Pro-Thr-Ala Tyr-Arg-Tyr, Leu-Pro-Thr, Tyr-Leu [67] H-Cys-Arg-Tyr-Leu-Pro-Thr-Ç ¹¹¹¹¹¹¹¹¹¹¹¹¹¹¹º ys-OH, [79] Arg-Tyr-Leu-Pro Phe(p-NH 2 )-Leu-Pro-Thr, [69,74] Phe(p-NO 2 )-Leu-Pro-Thr, Phe(3-CO 2 Et,4-OMe)-Leu-Pro-Thr Arg-D-Tyr-Leu-D-Pro-Thr, [83,91] Arg-Tyr-D-Leu-D-Pro-Thr [27] sag [51] sag [51] np ag [78] np np Phe(OEt) -ag [69] in [69] np sag [69] Phe(p-NH 2 ) -sag [51] sag [51] ag [77] ag [78] sag [69] ag [77] Phe(p-NO 2 ) -sag [51] sag [51] ag [78] ag [31] -Phe(p-NMe 2 ) -sag [51] ag [51] ag [78] --Dopa -sag [85] ag [76] ag [85] ag [78] wag [55] ag [76] Tyr(m-NH 2 ) -ag [31] ag [31] - [Orn(iPr) 1 ]...…”

“…Similar species specificity was noticed for [Tyr(m-NO 2 ) 2 ]-proctolin, which accelerated P. americana heart contractions but did not have any effect on the heart-beat frequency of T. molitor. On the other hand, [Tyr(m-NH 2 ) 2 ]-proctolin has proctolin activity against the heart of both insect species [31] and the locust oviduct [78]. For [Cha(4-OMe) 2 ]-proctolin [54] and [Afb(p-X) 2 ]-proctolin, where X = -OH, -NH 2, or -NO 2 , no cardiotropic action was observed in P. americana and T. molitor heart.…”

Proctolin in the post-genomic era: new insights and challenges

“…It is generally agreed that activation of the proctolin receptor on the surface of target cells leads to an increase in the intracellular levels of calcium by an IP3-mediated mechanism and by promoting the entry of extracellular calcium (Baines et al 1990;Hinton and Osborne 1995;Hinton et al 1998). Pharmacological evidence suggests the existence of at least two proctolin receptor subtypes in the foregut and extensor tibiae muscle of the locust, S. gregaria (Baines et al 1996;Hinton et al 1996), and in different tissues of the cockroach, Blaberus craniifer (Mazzocco-Manneval et al 1998). Numerous structure/activity studies conducted using contractions of the foregut, hindgut, oviduct and heart-beat frequency to bioassay proctolin analogues have identified many peptide agonists and several antagonists (Konopinska and Rosinski 1999).…”