Myotropic Peptides Research Articles

Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders.

Bioengineering of viral vectors for therapeutic gene delivery is a pivotal strategy to reduce doses, facilitate manufacturing, and improve efficacy and patient safety. Here, we engineered myotropic adeno-associated viral (AAV) vectors via a semirational, combinatorial approach that merges AAV capsid and peptide library screens. We first identified shuffled AAVs with increased specificity in the murine skeletal muscle, diaphragm, and heart, concurrent with liver detargeting. Next, we boosted muscle specificity by displaying a myotropic peptide on the capsid surface. In a mouse model of X-linked myotubular myopathy, the best vectors—AAVMYO2 and AAVMYO3—prolonged survival, corrected growth, restored strength, and ameliorated muscle fiber size and centronucleation. In a mouse model of Duchenne muscular dystrophy, our lead capsid induced robust microdystrophin expression and improved muscle function. Our pipeline is compatible with complementary AAV genome bioengineering strategies, as demonstrated here with two promoters, and could benefit many clinical applications beyond muscle gene therapy.

Identification of a new myotropic decapeptide from the skin secretion of the red-eyed leaf frog, Agalychnis callidryas.

Bradykinin-related peptides (BRPs) family is one of the most significant myotropic peptide families derived from frog skin secretions. Here, a novel BRP callitide was isolated and identified from the red-eyed leaf frog, Agalychnis callidryas, with atypical primary structure FRPAILVRPK-NH2. The mature peptide was cleaved N-terminally at a classic propeptide convertase cleavage site (-KR-) and at the C-terminus an unusual -GKGKGK sequence was removed using the first G residue as an amide donor for the C-terminally-located K residue. Thereafter, the synthetic replicates of callitide were assessed the myotropic activity and showed a significant contraction of balder, with the 0.63 nM EC50 value, more potent than most discovered myotropic peptides. The binding mode was further speculated by molecular docking and stimulation. The result indicated that the C-terminal of callitide might selectively bind to bradykinin receptor B2 (BKRB2). Further investigation of the callitide needs to be done in the future to be exploited as potential future drug leads.

Shrimp by-product hydrolysate induces intestinal myotropic activity in European seabass (Dicentrarchus labrax)

The transit time of feed through the digestive tract of fish is very important in fish culture because it can impact fish feeding rates and growth rates, and feed utilization. We identified a myotropic peptide in a shrimp (Litopenaeus vannamei) hydrolysate used in aquaculture fish feeds. It is a new pentapeptide (KNPEQ) cleaved from crustacean hemocyanin, that does not share sequence homology with peptides known to have myotropic activity in fish. We monitored the effect of this hydrolysate in European seabass (Dicentrarchus labrax), (i) in vivo during a feeding trial with low fish meal diets including shrimp hydrolysate, and (ii) in vitro on isolated intestine perfused with hydrolysate extracts. The dietary shrimp hydrolysate accelerated feces emission and led to contractions in perfused intestine. Different steps of purification of shrimp hydrolysate by reverse phase high performance liquid chromatography coupled with intestine in vitro assay were applied in order to purify the myotropic peptide. The sequence of the peptide was determined using both Edman degradation and mass spectrometry fragmentation. We confirmed then in vitro that the KNPEQ-mimetic peptide stimulated the contraction of the intestine in a transient manner at concentrations of 1 and 10 μM, and for >10 h at a concentration of 100 μM.

Identification of a Novel Vasodilatory Octapeptide from the Skin Secretion of the African Hyperoliid Frog, Kassina senegalensis

The defensive skin secretions of amphibians continue to be an excellent source of novel biologically-active peptides. Here we report the identification and pharmacological activity of a novel C-terminally amided myotropic octapeptide from the skin secretion of the African hyperoliid frog, Kassina senegalensis. The 8-amino acid peptide has the following primary structure: WMSLGWSL-amide and has a molecular mass of 978 Da. The primary structure and organisation of the biosynthetic precursor of WL-8 amide was successfully deduced from cloned skin secretion-derived cDNA. The open-reading frame encoded a single copy of WL-8, located at the C-terminus. Synthetic WL-8 amide was found to cause relaxation of rat tail artery smooth muscle with an EC50 of 25.98 nM. This peptide is unique in terms of its primary structure and is unlike any other peptide previously isolated from an amphibian source which has been archived in the NCBI database. WL-8 amide thus represents the prototype of a novel family of myotropic peptide from amphibian defensive skin secretions.

Balteatide: a novel antimicrobial decapeptide from the skin secretion of the purple-sided leaf frog, Phyllomedusa baltea.

The skin secretions of Neotropical phyllomedusine leaf frogs have proven to be a rich source of biologically active peptides, including antimicrobials. The major families of antimicrobial peptides (AMPs) reported are the dermaseptins and phylloseptins and the minor families are the dermatoxins, phylloxins, plasticins, distinctins, and medusins. Here, we report a novel AMP of 10 amino acid residues (LRPAILVRIKamide), named balteatide, from the skin secretion of wild Peruvian purple-sided leaf frogs, Phyllomedusa baltea. Balteatide was found to exhibit a 90% sequence identity with sauvatide, a potent myotropic peptide from the skin secretion of Phyllomedusa sauvagei. However, despite both peptides exhibiting only a single amino acid difference (I/T at position 9), sauvatide is devoid of antimicrobial activity and balteatide is devoid of myotropic activity. Balteatide was found to have differential activity against the Gram-positive bacterium, Staphylococcus aureus; the Gram-negative bacterium, Escherichia coli; and the yeast, Candida albicans, and unusual for phyllomedusine frog skin AMPs, was most potent (MIC 32 mg/L) against the yeast. Balteatide was also devoid of haemolytic activity up to concentrations of 512 mg/L. Phyllomedusine frog skin secretions thus continue to provide novel AMPs, some of which may provide templates for the rational design of new classes of anti-infective therapeutics.

A novel frog skin peptide containing function to induce muscle relaxation

A novel bioactive peptide (polypedarelaxin 1) was identified from the skin secretions of the tree frog, Polypedates pingbianensis. Polypedarelaxin 1 is composed of 21 amino acid residues with a sequence of QGGLLGKVSNLANDALGILPI. Its primary structure was further confirmed by cDNA cloning and mass spectrometry analysis. Polypedarelaxin 1 was found to elicit concentration-dependent relaxation effects on isolated rat ileum. It has no antimicrobial and serine protease inhibitory activities. BLAST search revealed that polypedarelaxin 1 did not show similarity to known proteins or peptides. Especially, polypedarelaxin 1 do not contain conserved structural motifs of other amphibian myotropic peptides, such as bradykinins, bombesins, cholecystokinin (CCK), and tachykinins, indicating that polypedarelaxin 1 belongs to a novel family of amphibian myotropic peptide.

A novel myotropic peptide from the skin secretions of the tree frog, Polypedates pingbianensis

A novel myotropic peptide, polypedatein, was purified and characterized from the skin secretions of the tree frog, Polypedates pingbianensis. Its primary structure, TLLCKYFAIC, was determined by Edman degradation and mass spectrometry. Polypedatein was subjected to bioassays including myotropic, antimicrobial, and serine protease inhibitory activities, which are related with many amphibian skin bioactive peptides. It was found to elicit concentration-dependent contractile effects on isolated rat ileum. cDNA clones encoding the precursor of polypedatein were isolated by screening a skin cDNA library of P.pingbianensis and then sequenced. The amino acid sequence deduced from the cDNA sequences matches well with the result from Edman degradation. BLAST search revealed that the sequence of polypedatein did not show similarity to known protein or peptide sequences. Especially, polypedatein does not contain conserved structural motifs of other amphibian myotropic peptides, such as bradykinins, bombesins, cholecystokinin (CCK), and tachykinins, indicating that polypedatein belongs to a novel amphibian myotropic peptide family. The signal peptide of the precursor encoding polypedatein shows significant sequence identity to that of other amphibian skin defensive peptides, such as antimicrobial peptides, bradykinins, lectins, and serine protease inhibitors, suggesting that polypedatein belongs to a novel amphibian myotropic peptide family. Polypedatein is also the first bioactive peptide from the genus of the frog, Polypedates.

GK-22 amide: a novel myotropic peptide from the skin secretion of the bamboo leaf odorous frog, Odorrana versabilis

GK-22 amide: a novel myotropic peptide from the skin secretion of the bamboo leaf odorous frog, Odorrana versabilis

Comparison of proctolin and FMRFamide actions on the motility of male and female beetle reproductive tracts

Two myotropic peptides, proctolin and FMRFamide, were tested for their action on the frequency of contractions of the the male ejaculatory duct and female oviduct of two beetle species: Tenebrio molitor and Zophobas atratus. The tested peptides caused changes in endogenous contraction frequencies of the reproductive tracts in both species. Proctolin exerted a strong stimulatory effect on spontaneous muscular contractions of the ejaculatory ducts and oviducts of T. molitor and Z. atratus. FMRFamide action, however, differed between species and organ tested. At high doses (10−7–10−5 M) it stimulated oviduct contractions in Z. atratus but inhibited the T. molitor oviduct contractility. In T. molitor, the peptide had a stimulatory effect on oviduct contractions at low doses (10−11–10−9 M). In contrast to proctolin, FMRFamide is a weak inhibitor of the ejaculatory ducts of both beetles at high concentrations (10−6–10−5 M). Differentiated responses of the ejaculatory ducts and oviducts of T. molitor and Z. atratus suggest that these peptides are functional and specific regulators of both reproductive tracts.

Sauvatide – A novel amidated myotropic decapeptide from the skin secretion of the waxy monkey frog, Phyllomedusa sauvagei

Here we describe the structural and functional characterization of a novel myotropic peptide, sauvatide, from the skin secretion of the waxy monkey frog, Phyllomedusa sauvagei. Sauvatide is a C-terminally amidated decapeptide with the following primary structure – LRPAILVRTKamide – monoisotopic mass 1164.77 Da, which was found to contract the smooth muscle of rat urinary bladder with an EC 50 of 2.2 nM. The sauvatide precursor, deduced from cloned skin cDNA, consists of 62 amino acid residues with a single copy of sauvatide located near the C-terminus. The mature peptide is generated from the precursor by cleavage at a classical –KR-cleavage site located proximal to the N-terminus and by removal of a –GKGK sequence at the C-terminus, the first glycyl residue acting as amide donor. Amphibian skin secretions thus continue to be a source of novel and potent biologically active peptides acting through functional targets in mammalian tissues.

Neuroendocrine and cytolytic peptides in frog skin: what do they all mean?

Event Abstract Back to Event Neuroendocrine and cytolytic peptides in frog skin: what do they all mean? Michael J. Conlon1* 1 United Arab Emirates University, Department of Biochemistry, Faculty of Medicine and Health Sciences, United Arab Emirates Cationic peptides with the propensity to adopt an amphipathic α-helical conformation in a membrane-mimetic environment are synthesized in the skins of many species of anurans (frogs and toads). These peptides frequently display potent cytolytic activities against a range of pathogenic bacteria and fungi consistent with the hypothesis that they play a role in the host’s system of innate immunity. Similarly, myotropic peptides in skin, such as tachykinins and bradykinins, are postulated to play a role in defending the animal against ingestion by predators. However, the importance of the peptides in the survival strategy of the animal is not clearly understood. The distribution of antimicrobial and neuroendocrine peptides among the different frog families is sporadic and many well-studied species in several families do not appear to synthesize these peptides. This suggests that production of dermal cytolytic and neuroendocrine peptides may offer some advantage to anurans in terms of natural selection but their precise biological function may need to be re-evaluated. Other biological activities demonstrated or suggested for these dermal peptides include regulation of apoptosis, particularly during metamorphosis, stimulation of chemotaxis of neutrophils, monocytes, and macrophages, enhancement of secretory phospholipase A2 activity, stimulation of insulin release from clonal ï€ β-cells, inhibition of neuronal nitric oxide synthase, regulation of ion- and water transport across the skin, and modification of male reproductive behaviour. Conference: 3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009. Presentation Type: Oral Presentation Topic: Symposium 12 – Comparative Neuroendocrinology: novel neurochemical systems Citation: Conlon MJ (2009). Neuroendocrine and cytolytic peptides in frog skin: what do they all mean?. Front. Neurosci. Conference Abstract: 3rd Mediterranean Conference of Neuroscience . doi: 10.3389/conf.neuro.01.2009.16.041 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Nov 2009; Published Online: 19 Nov 2009. * Correspondence: Michael J Conlon, United Arab Emirates University, Department of Biochemistry, Faculty of Medicine and Health Sciences, Al-Ain, United Arab Emirates, jmconlon1@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Michael J Conlon Google Michael J Conlon Google Scholar Michael J Conlon PubMed Michael J Conlon Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Allatotropin-related peptide in cockroaches: Identification via mass spectrometric analysis of single identified neurons

The first insect allatotropin-related peptide (ATRP) was isolated from head extracts of the adult sphinx moth Manduca sexta [Kataoka H, Toschi A, Li JP, Carney RL, Schooley DA, Kramer SJ. Identification of an allatotropin from adult Manduca sexta. Science 1989;243:1481–3.]. Meanwhile ATRPs are known from different holometabolous insects but only a single ATRP could be identified from hemimetabolous insects [Paemen L, Tips A, Schoofs L, Proost P, Van Damme J, De Loof A. Lom-AG-myotropin: a novel myotropic peptide from the male accessory glands of Locusta migratoria. Peptides 1991;12:7–10.]. This means that the extensive analysis of neuropeptides from Leucophaea maderae and Periplaneta americana, which led to the discovery of many novel insect neuropeptides, did not result in the detection of any ATRP. In this study, we used another approach to find a cockroach ATRP by first identifying Manse-AT immunoreactive neurons in the terminal ganglion that can be stained by retrograde labeling and are suitable for dissection and subsequent mass spectrometric analysis. The peptidomic analysis of these putative ATRP neurons paved the way for the identification of the first cockroach ATRP. MALDI-TOF/TOF tandem mass spectrometry revealed a sequence identity with Locmi-AG-MT-1 which classifies this ATRP as a highly conserved neuropeptide. A mass spectrometric screening of the nervous system allowed the detection of ATRP-ion signals in different parts of the CNS of P. americana as well as L. maderae. The data obtained in this study will be incorporated in a map of peptidergic neurons from the CNS of the American cockroach, P. americana.

An ontogenetic analysis of locustatachykinin-like expression in the central complex of the grasshopper Schistocerca gregaria

We have investigated the ontogenetic basis of locustatachykinin-like expression in a group of cells located in the pars intercerebralis of the grasshopper midbrain. These cells project fibers to the protocerebral bridge and the central body via a characteristic set of fiber bundles called the w, x, y, z tracts. Lineage analyses associate the immunoreactive cells with one of four neuroblasts (termed W, X, Y, Z) in each protocerebral hemisphere of the early embryo. Locustatachykinin is a ubiquitous myotropic peptide among the insects and its expression in the pars intercerebralis begins at approximately 60–65% of embryogenesis. This coincides with the appearance of the columnar neuroarchitecture characteristic of the central body. The number of immunoreactive cells in a given lineage is initially small, increases significantly in later embryogenesis, and attains the adult situation (about 7% of a lineage) in the first larval instar after hatching. Although each neuroblast generates progeny displaying a spectrum of cell body sizes, there is a clear morphological gradient, which reflects birth order within the lineage. Locustatachykinin expressing cells are located stereotypically at or near the tip of their lineage, which an age profile reveals places them amongst the first born progeny of their respective neuroblasts. Although these neuroblasts begin to generate progeny at approximately 25–27% of embryogenesis, their daughter cells remain quiescent with respect to locustatachykinin expression for over 30% of embryogenesis.

Ovarian and sperm regulatory peptides regulate ovulation in the oyster Crassostrea gigas

For more than six decades, several studies have shown that genital products to entering the mantle cavity via the incurrent siphon, initiate in oyster, strong and rhythmic contractions of the adductor muscle (AM). In order to characterize the regulatory peptides capable of triggering AM contractions, we focused on the identification of putative myotropic peptides from genital products. Two experimental approaches were developed. The first one, based on a mass spectrometry screening of the male genital products, led to the identification of the tetrapeptide APGWamide. This neuropeptide was also detected in the seminal secretions of the cephalopod Sepia officinalis. In this species, APGWamide is directly involved in the oocyte transport. In Crassostrea, in vitro bioassay demonstrated that APGWamide modulates the AM contractions that insure the release of oocytes in the external medium. Exposure of oysters to a physiological concentration of APGWamide triggered repetitive shell closures. The second experimental approach was based on the monitoring of HPLC purification by a myotropic bioassay using the cuttlefish oviduct contractions as a target. The successive purification steps of the acidic extraction of ovaries from mature female oysters, led to the characterization of the hexapeptide PIESVD. When applied to mature female oysters, this peptide triggered the increase of shell closure frequency. The activity of these two regulatory peptides is the first experimental evidence of a peptidergic control of egg-laying in oyster. APGWamide and PIESVD could be used, in commercial and experimental hatcheries, for the identification of mature females to be selected for in vitro fertilization.

Transgenic expression in tobacco of a poly-proctolin construct leading to production of the bioactive peptide

Short peptides can be expressed in plants using synthetic genes encoding multiple copies of the peptide spaced by dibasic endoproteolytic cleavage sites. A synthetic gene encoding an array of repeated copies of proctolin, a very well characterized insect myotropic peptide, spaced by Arg residues, was synthesized and expressed in tobacco plants. The successful production of bioactive proctolin from the precursor in transgenic plants was demonstrated by immunoblot, HPLC, mass spectrometry and a bioassay based on the contraction of isolated cockroach hindgut. These results suggest that in planta, as in animals and yeasts, endopeptidases of the serine proteases family may be involved in precursor processing.

Myotropic effect of helicokinins, tachykinin-related peptides and Manduca sexta allatotropin on the gut of Heliothis virescens (Lepidoptera: Noctuidae)

Different insect neuropeptides (helicokinins, tachykinin-related and allatoregulating peptides) were investigated with regard to their myostimulatory effects using whole-gut preparations isolated from fifth instar Heliothis virescens larvae. The experiments demonstrated that representatives of all three peptide families are able to induce and amplify gut contractions in this species in a dose-dependent manner. Structure–activity studies (alanine scan, d-amino acid scan and truncated analogues) with the helicokinin Hez-K1 supported the finding, that the core sequence for biological activity of kinins is the amidated C-terminal pentapeptide (FSPWG-amide). Similar investigations with insect tachykinin isolated from Leucophaea madera (Lem-TRP1) revealed that the minimum sequence evoking a physiological gut response in H. virescens is the amidated hexapeptide (GFLGVR-amide), which represents the conserved amino acid sequence for Leucophaea TRPs in general. The peptide concentration causing a half-maximal gut contraction (EC 50) for Lem-TRP1 was about 26 nM. Although the potency of Lem-TRP1 was 9-fold lower compared with Hez-KI (EC 50: 3 nM), the maximal tension of the gut obtained with Lem-TRP1 was 1.7-fold higher compared with Hez-KI. The EC 50 of Manduca sexta allatotropin (Mas-AT; 79 nM) was of lowest potency among all three peptides tested. In a pharmacological study, co-incubation experiments with Lem-TRP1, Hez-KI or Mas-AT and compounds interfering with signal transduction pathways were employed to investigate the mode of action of the myotropic effects of these peptides. Cadmium and the protein kinase C (PKC) inhibitor tamoxifen attenuated the contractile effects of all three peptides tested. The data suggest that in the gut muscle of H. virescens the myotropic peptides bind to G-protein-coupled receptors that cause contraction by promoting the entry of extracellular calcium mediated by a PKC involved pathway.

Isolation, identification, and synthesis of a disulfated sulfakinin from the central nervous system of an arthropods the white shrimp Litopenaeus vannamei

Two myotropic peptides displaying tyrosyl sulfation have been isolated from an extract of central nervous systems (brain, suboesophageal ganglion, thoracic ganglia, and ventral nerve cord) of the white shrimp Litopenaeus vannamei. Both peptides were identified by mass spectrometry and belong to the sulfakinin family of neuropeptides, which are characterized by the C-terminal hexapeptide Y(SO 3H)GHMRF-NH 2 preceded by two acidic amino acid residues. Pev-SK 1 (AGGSGGVGGEY(SO 3H)DDY(SO 3H)GH(L/I) RF-NH 2) has two sulfated tyrosyl residues and a unique (L/I) for M substitution in the C-terminal sequence. Pev-SK 2 (pQFDEY(SO 3H)GHMRF-NH 2) fully complies with the typical sulfakinin core sequence and is blocked by a pyroglutamyl residue. Synthetic analogs (sulfated and unsulfated) were synthesized and the tyrosyl sulfations were confirmed by myotropic activity studies and co-elution with the native fractions. Pev-SK 1 is the first disulfated neuropeptide elucidated in the phylum of the arthropoda, with the only other reported disulfated neuropeptide, called cionin, found in a protochordate. The similarities in amino acid sequence and posttranslational modifications of the crustacean sulfakinins and protochordate cionin provide further evidence for the hypothesis stating that gastrin/CCK, cionin, and sulfakinins originate from a common ancestral gastrin/CCK-like peptide.

Activity of crustacean myotropic neuropeptides on the oviduct and hindgut of the crayfish Astacus leptodactylus

Summary In crustaceans, a large number of peptides have been identified because of their effect on visceral muscles. Predominantly the heart and the hindgut have been used to purify myotropic peptides from crustaceans. Lately, a number of myotropins were purified from the central nervous system of crustaceans through their ability to induce Leucophaea maderae hindgut contraction. Pev-tachykinin, Pev-SK 2, Pev-kinins 1–6 and Pev-PK 1 and 2 were tested on their ability to affect the contractility of the crayfish (Astacus leptodactylus) oviduct and hindgut. We have demonstrated for the first time that the muscular sheath surrounding the crayfish oviduct is a possible target for myotropic neuropeptides. The crustacean myokinins (Pev-kinins 1–6) were able to increase the basal tonus of the crustacean oviduct. The other tested myotropins were inactive in this bioassay. Pev-kinins proved to be potent stimulators of crayfish hindgut contraction, this in contrast to Pev-tachykinin and Pev-SK 2.

THE EFFECTS OF THREE DROSOPHILA MELANOGASTER MYOTROPINS ON THE FREQUENCY OF FOREGUT CONTRACTIONS DIFFER

Myotropic peptides can be grouped into different families based on their structure. Three Drosophila melanogaster myotropin families are represented by TDVDHVFLRFamide, dromyosuppressin (DMS), pEVRYRQCYFNPISCF, an allatostatin C-type peptide named flatline (FLT), and SDNFMRfamide, a FMRFamide, a FMRFamide-containing peptide. The structures of DMS, FLT, and SDNFMRFamide differ and each peptide is encoded by a different gene. In addition, the spatial and temporal distributions of DMS, FLT, and SDNFMRFamide are dissimilar. DMS, FLT, and SDNFMRFamide each decreases heart rate; however, their effects are profoundly different. Likewise, the effects of these three myotropins on the frequency of the spontaneous contractions of the crop, an anterior portion of the foregut, differ. DMS stops crop movement without recovery for at least 10-min period after applying the peptide, FLT significantly decreases the frequency of spontaneous contractions, but its effect partially reverses within a few minutes after applying the peptide, and SDNFMRFamide only slightly decreased crop motility, an effect that was not significantly different from the effect of saline. The differences in the structures, distributions, and activities of DMS, FLT, and SDNFMRFamide suggest their synthesis and release are under different sensory inputs and regulatory mechanisms, and that roles in affecting the frequency of crop contractions differ.

Myotropic Peptides in Drosophila Melanogaster And The Genes That Encode Them

Myotropic peptides are structurally dissimilar; thus, they comprise different families. The cellular expressions of myotropins suggest they act as hormones, transmitters, and modulators of numerous biological processes. Drosophila melanogaster allatostatin (AST), FMRFamide-containing, dromyosuppressin (DMS), and drosulfakinin (DSK) peptides represent four different myotropin families. A different gene encodes each of these four myotropin families. D. melanogaster AST, FMRFamide-containing, DMS, and DSK peptides are present in neural and gut tissue, but are not all expressed in the same cells. These four families of myotropins affect spontaneous contractions of gut, heart, and/or reproductive tissue, but their effects are dissimilar in magnitude and time course. Based on their structures, genes, distributions, and activities, the synthesis and release of these D. melanogaster myotropins are likely governed by different sensory inputs and regulatory mechanisms. The differences in structures, precursors, cellular expressions, and activities are consistent with the conclusion that they do not play redundant roles in their effects on the frequency of muscle contractions. Orthologs of these D. melanogaster myotropins exist in other animal species; thus, research on the mechanisms involved in their production and processing, functions, and signaling may be widely applicable. Here, we review research on D. melanogaster AST, FMRFamide-containing, myosuppressin, and sulfakinin peptides.