Crustacean neuropeptides: Structures,functions and comparative aspects

In this article, an attempt is made to review the presently known, completely identified crustacean neuropeptides with regard to structure, function and distribution. Probably the most important progress has been made in the elucidation of a novel family of large peptides from the X-organ-sinus gland system which includes crustacean hyperglycemic hormone (CHH), putative molt-inhibiting hormone (MIH) and vitellogenesis (=gonad)-inhibiting hormone (VIH). These peptides have so far only been found in crustaceans. Renewed interest in the neurohemal pericardial organs has led to the identification of a number of cardioactive/myotropic neuropeptides, some of them. unique to crustaceans. Important contributions have been made by immunocytochemical mapping of peptidergic neurons in the nervous system, which has provided evidence for a multiple role of several neuropeptides as neurohormones on the one hand and as local transmitters or modulators on the other. This has been corroborated by physiological studies. The long-known chromatophore-regulating hormones, red pigment concentrating hormone (RPCH) and pigment-dispending hormone (PDH), have been placed in a broader perspective by the demonstration of an additional role as local neuromodulators. The scope of crustacean neuropeptide research has thus been broadened considerably during the last years.     

Crustacean neuropeptides

Crustaceans have long been used for peptide research. For example, the process of neurosecretion was first formally demonstrated in the crustacean X-organ–sinus gland system, and the first fully characterized invertebrate neuropeptide was from a shrimp. Moreover, the crustacean stomatogastric and cardiac nervous systems have long served as models for understanding the general principles governing neural circuit functioning, including modulation by peptides. Here, we review the basic biology of crustacean neuropeptides, discuss methodologies currently driving their discovery, provide an overview of the known families, and summarize recent data on their control of physiology and behavior.     

Physiological arousal: a role for hypothalamic systems

The lateral hypothalamus (LH) has long been known as a homeostasis center of the brain that modulates feeding behavior, arousal and reward. The hypocretins (Hcrts, also called orexins) and melanin-concentrating hormone (MCH) are neuropeptides produced in two intermingled populations of a few thousand neurons in the LH. The Hcrts have a prominent role in regulating the stability of arousal, since Hcrt system deficiency leads to narcolepsy. MCH is an important modulator of energy balance, as MCH system deficiency in mice leads to leanness and increased metabolism. Recently, MCH has been proposed to modulate rapid eye movement sleep in rodents. In this review, we propose a working model of the cross-talk between Hcrt and MCH circuits that may provide an arousal balance system to regulate complex goal-oriented behaviors.     

Peptides in the mammalian cardiovascular system

Summary Ample immunocytochemical evidence is now available demonstrating that several peptides are present in the mammalian cardiovascular system where they are localised to nerve fibres and myocardial cells. The neuropeptides (neuropeptide Y, calcitonin gene-related peptide, tachykinins and vasoctive intestinal polypeptide) are localised to large secretory vesicles in subpopulations of afferent or efferent nerves supplying the heart and vasculature of several mammals, including man. Although they often exert potent pharmacological effects on the tissues in which they occur their physiological significance has still to be established. They may act directly via specific receptors and/or indirectly by influencing the release and action of other cardiovascular transmitters. In marked contrast, atrial natriuretic peptide is produced by cardiac myocytes and considered to act as a circulating hormone.     

Peptides in the mammalian cardiovascular system

Ample immunocytochemical evidence is now available demonstrating that several peptides are present in the mammalian cardiovascular system where they are localised to nerve fibres and myocardial cells. The neuropeptides (neuropeptide Y, calcitonin gene-related peptide, tachykinins and vasoactive intestinal polypeptide) are localised to large secretory vesicles in subpopulations of afferent or efferent nerves supplying the heart and vasculature of several mammals, including man. Although they often exert potent pharmacological effects on the tissues in which they occur their physiological significance has still to be established. They may act directly via specific receptors and/or indirectly by influencing the release and action of other cardiovascular transmitters. In marked contrast, atrial natriuretic peptide is produced by cardiac myocytes and considered to act as a circulating hormone.     

Characterization of a set of abdominal neuroendocrine cells that regulate stress physiology using colocalized diuretic peptides in <Emphasis Type="Italic">Drosophila</Emphasis>

Multiple neuropeptides are known to regulate water and ion balance in Drosophila melanogaster. Several of these peptides also have other functions in physiology and behavior. Examples are corticotropin-releasing factor-like diuretic hormone (diuretic hormone 44; DH44) and leucokinin (LK), both of which induce fluid secretion by Malpighian tubules (MTs), but also regulate stress responses, feeding, circadian activity and other behaviors. Here, we investigated the functional relations between the LK and DH44 signaling systems. DH44 and LK peptides are only colocalized in a set of abdominal neurosecretory cells (ABLKs). Targeted knockdown of each of these peptides in ABLKs leads to increased resistance to desiccation, starvation and ionic stress. Food ingestion is diminished by knockdown of DH44, but not LK, and water retention is increased by LK knockdown only. Thus, the two colocalized peptides display similar systemic actions, but differ with respect to regulation of feeding and body water retention. We also demonstrated that DH44 and LK have additive effects on fluid secretion by MTs. It is likely that the colocalized peptides are coreleased from ABLKs into the circulation and act on the tubules where they target different cell types and signaling systems to regulate diuresis and stress tolerance. Additional targets seem to be specific for each of the two peptides and subserve regulation of feeding and water retention. Our data suggest that the ABLKs and hormonal actions are sufficient for many of the known DH44 and LK functions, and that the remaining neurons in the CNS play other functional roles.     

Biology of the CAPA peptides in insects

CAPA peptides have been isolated from a broad range of insect species as well as an arachnid, and can be grouped into the periviscerokinin and pyrokinin peptide families. In insects, CAPA peptides are the characteristic and most abundant neuropeptides in the abdominal neurohemal system. In many species, CAPA peptides exert potent myotropic effects on different muscles such as the heart. In others, including blood-sucking insects able to transmit serious diseases, CAPA peptides have strong diuretic or anti-diuretic effects and thus are potentially of medical importance. CAPA peptides undergo cell-type-specific sorting and packaging, and are the first insect neuropeptides shown to be differentially processed. In this review, we discuss the current knowledge on the structure, distribution, receptors and physiological actions of the CAPA peptides. Received 28 April 2006; received after revision 5 June 2006; accepted 4 July 2006     

Regulatory peptides in the respiratory system

Many regulatory peptides have been described in the respiratory tract of animals and humans. Some peptides (bombesin, calcitonin, calcitonin gene-related peptide) are localised to neuroendocrine cells and may have a trophic or transmitter role. Others are localised to motor nerves. Vasoactive intestinal peptide and peptide histidine isoleucine are candidates for neurotransmitters of non-adrenergic inhibitory fibres and may be cotransmitters in cholinergic nerves. These peptides may regulate airway smooth muscle tone, bronchial blood flow and airway secretions. Sensory neuropeptides (substance P, neurokinin A and B, calcitonin gene-related peptide) may contract airway smooth muscle, stimulate mucus secretion and regulate bronchial blood flow and microvascular permeability. If released by an axon reflex mechanism these peptides may be involved in the pathogenesis of asthma. Other peptides, such as galanin and neuropeptide Y, are also present but their function is not yet known.     

Regulatory peptides in the respiratory system

Summary Many regulatory peptides have been described in the respiratory tract of animals and humans. Some peptides (bombesin, calcitonin, calcitonin gene-related peptide) are localised to neuroendocrine cells and may have a trophic or transmitter role. Others are localised to motor nerves. Vasoactive intestinal peptide and peptide histidine isoleucine are candidates for neurotransmitters of non-adrenergic inhibitory fibres and may be cotransmitters in cholinergic nerves. These peptides may regulate airway smooth muscle tone, bronchial blood flow and airway secretions. Sensory neuropeptides (substance P, neurokinin A and B, calcitonin gene-related peptide) may contract airway smooth muscle, stimulate mucus secretion and regulate bronchial blood flow and microvascular permeability. If released by an axon reflex mechanism these peptides may be involved in the pathogenesis of asthma. Other peptides, such as galanin and neuropeptide Y, are also present but their function is not yet known.     

Neuropeptides in pelvic afferent pathways

Neurochemical and pharmacological experiments have raised the possibility that several neuropeptides including, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI), substance P, calcitonin gene-related peptide (CGRP), neurokinin A, cholecystokinin (CCK) and opioid peptides may be transmitters in afferent pathways to the pelvic viscera. These substances are widely distributed in: 1) nerve fibers in the pelvic organs, 2) visceral afferent neurons in the lumbosacral dorsal root ganglia and 3) at sites of afferent termination in the spinal cord. Double staining immunocytochemical techniques have shown that more than one peptide can be localized in individual visceral afferent neurons and that neuronal excitatory (VIP, substance P, CCK) and inhibitory peptides (leucine enkephalin) can coexist in the same afferent cell. Studies with the neurotoxin, capsaicin, indicate that peptidergic afferent pathways are involved in the initiation of central autonomic reflexes as well as peripheral axon reflexes which modulate smooth muscle activity, facilitate transmission in automatic ganglia and trigger local inflammatory responses.     

Neuropeptides in pelvic afferent pathways

Summary Neurochemical and pharmacological experiments have raised the possibility that several neuropeptides including, vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI), substance P, calcitonin gene-related peptide (CGRP), neurokinin A, cholecystokinin (CCK) and opioid peptides may be transmitters in afferent pathways to the pelvic viscera. These substances are widely distributed in: 1) nerve fibers in the pelvic organs, 2) visceral afferent neurons in the lumbosacral dorsal root ganglia and 3) at sites of afferent termination in the spinal cord. Double, staining immunocytochemical techniques have shown that more than one peptide can be localized in individual visceral afferent neurons and that neuronal excitatory (VIP, substance P, CCK) and inhibitory peptides (leucine enkephalin) can coexist in the same afferent cell. Studies with the neurotoxin, capsaicin, indicate that peptidergic afferent pathways are, involved in the initiation of central autonomic reflexes as well as peripheral axon reflexes which modulate smooth muscle activity, facilitate transmission in automatic ganglia and trigger local inflammatory responses.     

Coexistence of peptides with classical neurotransmitters

In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, gamma-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than one messenger molecule. The exact functional role of such coexisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more complex than perhaps hitherto assumed.     

Neuropeptides and the microcircuitry of the enteric nervous system

Summary The discovery of neuropeptides in enteric neurons has revolutionized the study of the microcircuitry of the enteric nervous system. Form immunohistochemistry, it is now clear that some individual enteric neurons contain several different neuropeptides with or without other transmitter-specific markers and that these markers occur in various combinations. There is evidence from experiments in which nerve pathways are interrupted that populations of enteric neurons with different combinations of markers have different projection patterns, sending their processes to distinct targets using different routes. Correlations between the neurochemistry of enteric neurons and the types of synaptic inputs they receive are also beginning to emerge from electrophysiological studies. These findings imply that enteric neurons are chemically coded by the combinations of peptides and other transmitter-related substances they contain and that the coding of each population correlates with its role in the neuronal pathways that control gastrointestinal function.     

Neuropeptides and the microcircuitry of the enteric nervous system

The discovery of neuropeptides in enteric neurons has revolutionized the study of the microcircuitry of the enteric nervous system. From immunohistochemistry, it is now clear that some individual enteric neurons contain several different neuropeptides with or without other transmitter-specific markers and that these markers occur in various combinations. There is evidence from experiments in which nerve pathways are interrupted that populations of enteric neurons with different combinations of markers have different projection patterns, sending their processes to distinct targets using different routes. Correlations between the neurochemistry of enteric neurons and the types of synaptic inputs they receive are also beginning to emerge from electrophysiological studies. These findings imply that enteric neurons are chemically coded by the combinations of peptides and other transmitter-related substances they contain and that the coding of each population correlates with its role in the neuronal pathways that control gastrointestinal function.     

Neuropeptides of the silkworm, Bombyx mori.

Six neuropeptides of the silkworm, Bombyx mori, have been isolated and chemically characterized during the past 10 years. They are bombyxin, prothoracicotropic hormone, pheromone-biosynthesis-activating neuropeptide/melanization-and-reddish-coloration hormone, diapause hormone, eclosion hormone, and adipokinetic hormone. Recent progress in research on these neuropeptides is described.     

Coexistence of peptides with classical neurotransmitters

Summary In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, -aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than the one messenger molecule. The exact functional role of such coesisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more compex than perhaps hitherto assumed.     

Neuropeptides of the silkworm,Bombyx mori

Six neuropeptides of the silkworm,Bombyx mori, have been isolated and chemically characterized during the past 10 years. They are bombyxin, prothoracicotropic hormone, pheromone-biosynthesis-activating neuropeptide/melanization-and-reddish-coloration hormone, diapause hormone, eclosion hormone, and adipokinetic hormone. Recent progress in research on these neuropeptides is described.     

Galanin – 25 years with a multitalented neuropeptide

The skin, the largest organ of the body, functions as a barrier between the body proper and the external environment, as it is constantly exposed to noxious stressors. During the last few years, the concept of an interactive network involving cutaneous nerves, the neuroendocrine axis, and the immune system has emerged. The neuroendocrine system of the skin is composed of locally produced neuroendocrine mediators that interact with specific receptors. Among these mediators are neuropeptides, including members of the galanin peptide family--galanin, galanin-message-associated peptide, galanin-like peptide, and alarin--which are produced in neuronal as well as nonneuronal cells in the skin. Here we review the expression of the galanin peptides and their receptors in the skin, and the known functions of galanin peptides in different compartments of the skin. We discuss these data in light of the role of the galanin peptide family in inflammation and cell proliferation.     

Penaeidins, a family of antimicrobial peptides from penaeid shrimp (Crustacea, Decapoda)

The production of antimicrobial peptides represents a first-line host defense mechanism of innate immunity that is widespread in nature. Only recently such effectors were isolated in crustacean species, whereas numerous antimicrobial peptides have been characterized from other arthropods, both insects and chelicerates. This review presents findings on a family of antimicrobial peptides, named penaeidins, isolated from the shrimp Penaeus vannamei. Their structure and antimicrobial properties as well as their immune function will be discussed through analyses of penaeidin gene expression and peptide distribution upon microbial challenge. Received 21 January 2000; received after revision 10 March 2000; accepted 10 March 2000