Screening of antifeedant activity in brain extracts led to the identification of sulfakinin as a satiety promoter in the German cockroach.

Abstract

The feeding cycle of the adult female cockroach Blattella germanica parallels vitellogenesis. The study of the mechanisms that regulate this cycle led us to look for food-intake inhibitors in brain extracts. The antifeedant activity of brain extracts was tested in vivo by injecting the extract and measuring the carotenoids contained in the gut from carrot ingested after the treatment. By HPLC fractionation and tracking the biological activity with the carrot test, we isolated the sulfakinin EQFDDY(SO 3 H) GHMRFamide (Pea-SK). A synthetic version of the peptide inhibited food intake when injected at doses of 1 mg (50% inhibition) and 10 mg (60% inhibition). The sulfate group was required for food-intake inhibition. These biological and structural features are similar to those of the gastrincholecystokinin (gastrin-CCK) family of vertebrate peptides. However, heterologous feeding assays (human CCK-8 tested on B. germanica, and Pea-SK tested on the goldfish Carassius auratus ) were negative. In spite of this, alignment and cluster analysis of these and other structurally similar peptide families suggest that sulfakinins and gastrin -CCKs are homologous, and that mechanisms of feeding regulation involving these regulatory peptides may have been conserved during evolution between insects and vertebrates.Keywords: Blattella germanica; food-intake control; German cockroach; sulfakinin.How do insects regulate food intake and satiety? The answer holds an obvious academic interest, but it may also offer great potential for the design of new insecticides. Indeed, the induction of immediate satiety may prevent the attack of insects on our crops and stored food.In vertebrates, a variety of mechanisms are involved in the regulation of food intake and energy balance, for example, physiological signals such as neuronal inputs related to circadian rhythms, metabolic signals reflecting the rate of use of various energy sources by brain and abdominal viscera, gastrointestinal signals elicited by gastric distension, and the release of peptides from the gastrointestinal tract in response to nutrient ingestion that act on the brain [1,2]. Most of these factors are peptides, which may be peripheral, central or circulatory. Satiety factors include: the short-term and peripheral peptides cholecystokinin (CCK), bombesin, enterostatin and glucagon-like peptide-1; the central peptides corticotropin-releasing factor and melanocortin; and the long-term circulatory proteinaceous factor leptin. Conversely, hunger factors are central and include neuropeptide Y, galanin and orexin [3].The equivalent information has not been acquired for insects, although recent developments indicate that the endocrine regulation of physiological processes is at least as complex as in vertebrates. Therefore, thorough research in this field may unveil the factors involved in the presumably complex regulatory systems governing food intake in insects.The adult females of anautogenous insect species, which require food as a prerequisite for oogenesis, are suitable ex...

Identification and cardiotropic actions of sulfakinin peptides in the American lobster Homarus americanus

“…While not demonstrated directly, the distributions of sulfakinin-like immunoreactivity in many insects, particularly the dipterans, suggests a neuromodulatory role for this peptide family in the CNS (Duve et al, 1994;Davis et al, 1996;Nichols and Lim, 1996;East et al, 1997). Additionally, sulfakinins have been shown to stimulate the release of ␣-amylase from the midgut of both the weevil Rhynchophorus ferrugineus and the moth Opisina arenosella (Nachman et al, 1997;Harshini et al, 2002), and have been shown to be potent inhibitors of food intake in the locust Schistocerca gregaria, the cockroach Blatella germanica and the blowfly Phormia regina (Wei et al, 2000;Maestro et al, 2001;Downer et al, 2007).…”

“…As has been noted by many authors, the sulfakinins share structural similarities to members of the vertebrate cholecystokinin (CCK)/gastrin family of peptides (Table·1), as well as to cionin (Table·1), a disulfated peptide isolated from the protochordate tunicate Ciona intestinalis (Johnsen and Rehfeld, 1990). It is the belief of many that these structural similarities are the result of a common ancestry for the two groups of peptides (Nachman et al, 1986a;Nachman et al, 1986b;Nichols et al, 1988;Veenstra, 1989;Schoofs et al, 1990;Maestro et al, 2001;Torfs et al, 2001;Nachman et al, 2005). In addition to the observed sequence homologies, the hypothesis of a common ancestor for the CCK/gastrins and the sulfakinins is supported by the findings that both share a number of conserved functions: both groups are myoactive on the gut, induce the release of the enzyme amylase from the digestive system, and serve as satiety factors (Nachman et al, 1997;Wei et al, 2000;Maestro et al, 2001;Harashini et al, 2002;Downer et al, 2007).…”

“…First using biochemical methods, and more recently via molecular techniques, a number of sulfakinin isoforms have been identified from insects (Nachman et al, 1986a;Nachman et al, 1986b;Nichols et al, 1988;Veenstra, 1989;Schoofs et al, 1990;Fonagy et al, 1992;Nichols, 1992;Duve et al, 1995;Maestro et al, 2001) (NCBI accession number AY341429; NCBI accession number AY758365) (Table·1). In contrast, sulfakinin isoforms have thus far been biochemically isolated and characterized from just two crustaceans, the penaeid shrimp Penaeus monodon and Litopenaeus vannamei (Johnsen et al, 2000;Torfs et al, 2002) (Table·1).…”

“…1 This study; 2 (Johnsen et al, 2000); 3 (Torfs et al, 2002); 4 (Nachman et al, 1986a); 5 (Nachman et al, 1986b); 6 (Veenstra, 1989); 7 (Maestro et al, 2001); 8 (Nichols et al, 1988); 9 (Nichols, 1992); 10 (Fonagy et al, 1992); 11 (Duve et al, 1995); 12 NCBI accession number AY341429; 13 NCBI accession number AY758365; 14 (Schoofs et al, 1990); 15 (Johnsen and Rehfeld, 1990). The origin of the N-terminal pyro-residue in the short SK isoforms of shrimp was originally given as being derived from glutamine rather than glutamic acid (as our molecular analysis has shown is the case for the Hoa-SK I), though there is no data to prove this assignment currently.…”

Molecular physiology of crustacean and insect neuropeptides

“…83) They stimulate hindgut contraction in the cockroach, L. maderae, a amylase secretion in the midgut of the weevil, Rhynchophorus ferrugineus, 84) have a cardioacceleratory effect on Periplaneta, and reduced food intake in Schistocerca gregaria and Blatella germanica. 85) The Drosophila sulfakinin gene encodes a 128 amino-acid long protein processed into two GHMRFamide peptides (DSK I and II) and a peptide of unrelated sequence, DSK 0. 79) FLRFamides (also known as myosuppressins), are decapeptides with pleiotropic effects acting on a wide variety of organs.…”