Prolyl-threonine

1. The neuropeptide proctolin (Arg-Tyr-Leu-Pro-Thr) both potentiates neurally evoked contractions and causes contractures of insect skeletal muscle. In the hindleg extensor tibiae muscle of the locust, Schistocerca gregaria, the proctolin analogue [Afb (p-NO2)2]-proctolin is also able to potentiate neurally evoked contractions but is approximately 1,000-fold less effective in evoking contractures. 2. Proctolin and [Afb (p-NO2)2]-proctolin are equipotent in their ability to elevate the second-messenger inositol trisphosphate in isolated extensor tibiae muscle fiber membranes. 3. [Afb (p-NO2)2]-proctolin is approximately 1,000-fold less effective than proctolin in reducing the resting potassium conductance (GK) in extensor tibiae fibers. 4. We conclude that the action of proctolin on the extensor tibiae muscle is mediated by at least two receptor subtypes and that [Afb (p-NO2)2]-proctolin acts selectively on the receptor that potentiates neurally evoked contractions.

Methanolic head and brain extracts of the Colorado potato beetle contain several myotropins, active in the Locusta oviduct motility assay. Reversed phase high performance liquid chromatography (RP HPLC) gave evidence for the presence of three myotropic factors, with retention times close to that of proctolin. Both strongly stimulated the frequency, amplitude and tonus of the myogenic oviduct contractions. Gas phase sequencing and FAB-MS revealed that, besides proctolin (Arg-Tyr-Leu-Pro-Thr), two natural proctolin analogues were present. The first one is Ala-Tyr-Leu-Pro-Thr and is designed as Ala1-proctolin. The threshold concentration for biological activity of Ala1-proctolin was 10(-7) M, compared to 10(-10) M for proctolin itself. Ala1-proctolin is the first identified biological analogue of proctolin. The full nature of the first amino acid of a third proctolin-analogue (x-Tyr-Leu-Pro-Thr) is probably a modified amino acid of which the identity could as yet not be revealed. Our results suggest the existence of a family of proctolin-like peptides.