Comparative aspects of structure and action of molluscan neuropeptides

A number of neuropeptides were isolated from the ganglia and muscles of molluscs, and their actions were examined. Diverse neuropeptides, in addition to several classical neurotransmitters, were suggested to be involved in the regulation of the anterior byssus retractor muscle ofMytilus. A wide structural variety of members of theMytilus inhibitory peptide family was observed in each of the generaMytilus, Achatina andHelix. Gly-Trp-NH₂, the C-terminal dipeptide fragment of the neuropeptide AGPWamide, showed a more potent action than the parent peptide in all of the muscles examined. Peptides related to some molluscan neuropeptides were found to be distributed interphyletically. Some neuropeptides containing ad-amino acid residue were found inAchatina andMytilus. These aspects of molluscan neuropeptides are thought not to be exceptional.     

Inhibitory effect of beta-hydroxyglutamic acid on a molluscan giant neurone.

We found a spontaneously firing neurone, inhibited by beta-hydroxy(erythro)-L-glutamic acid, identified in the subesophageal ganglia of an African giant snail (Achatina fulica Férussac), although this neurone is not sensitive to L-glutamic acid. We suggest that beta-hydroxy(erythro)-L-glutamic acid may be a putative inhibitory synaptic transmitter of the identified molluscan neurone.     

Effects of physalaemin,a vase-active peptide from amphibian skin,on the excitability of an identifiable molluscan giant neurone ofAchatina fulica Férussac

Summary We examined effects of several vasoactive peptides (substance P, physalaemin, neurotensin, bradykinin, angiotensin etc.) on the excitability of molluscan giant neurones identified in the subesophageal ganglia ofAchatina fulica Férussac. Of these peptides, only physalaemin showed a remarkable excitatory effect on a giant tonically autoactive neurone.     

Effects of physalaemin, a vaso-active peptide from amphibian skin, on the excitability of an identifiable molluscan giant neurone of Achatina fulica Férussac.

We examined effects of several vasoactive peptides (substance P, physalaemin, neurotensin, bradykinin, angiotensin etc.) on the excitability of molluscan giant neurones identified in the subesophageal ganglia of Achatina fulica Férussac. Of these peptides, only physalaemin showed a remarkable excitatory effect on a giant tonically autoactive neurone.     

Calcium transients in a molluscan smooth muscle

Summary The changes in myoplasmic calcium concentration during contraction were recorded in the anterior byssal retractor muscle ofMytilus edulis using murexide as calcium indicator, and were found to be qualitatively similar to those in striated muscles except for their slow time course.     

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     

A review of the electrophysiological, pharmacological and single channel properties of heart ventricle muscle cells in the snail Lymnaea stagnalis.

Although a considerable body of information has accumulated describing the pharmacological properties of a wide range of molluscan muscle types, the physiological bases underlying these properties have not been thoroughly investigated. At present, little is known about the types of ion channels and their regulation in molluscan muscle cell membranes. Voltage-clamp, and more recently, patch-clamp techniques have revealed molluscan muscles possess a complex array of channel types with various pharmacological and electrophysiological properties. The gating properties of these channels and their modulation by chemical agents, however, are still poorly understood. This review summarizes some aspects of molluscan muscle function with particular reference to the heart ventricle muscle of the pond snail, Lymnaea stagnalis.     

A review of the electrophysiological,pharmacological and single channel properties of heart ventricle muscle cells in the snailLymnaea stagnalis

Although a considerable body of information has accumulated describing the pharmacological properties of a wide range of molluscan muscle types, the physiological bases underlying these properties have not been thoroughly investigated. At present, little is known about the types of ion channels and their regulation in molluscan muscle cell membranes. Voltage-clamp, and more recently, patch-clamp techniques have revealed molluscan muscles possess a complex array of channel types with various pharmacological and electrophysiological properties. The gating properties of these channels and their modulation by chemical agents, however, are still poorly understood. This review summarizes some aspects of molluscan muscle function with particular reference to the heart ventricle muscle of the pond snail,Lymnaea stagnalis.     

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.     

Tachykinins in regulation of gastric motility and secretion

The tachykinins constitute a family of neuropeptides with a common C-terminal amino acid sequence. The best known tachykinin is substance P. Tachykinins are found in the nerve plexuses and nerve fibers in the stomach of all species examined. The circular muscle layer is densely innervated, whereas the longitudinal layer and the mucosa are less intensively innervated. Tachykinins are also found in a significant number of afferent neurons with cell bodies in the dorsal root ganglia. Release of tachykinin can be demonstrated in response to both electrical stimulation of the vagus nerves and application of capsaicin. In the stomach all three known tachykinin receptors seem to be present. Although species variations exist, NK-2 receptors are generally present on the musculature, NK-1 receptors on both neurons and muscles, and NK-3 receptors on neurons only. Tachykinins stimulate motility in all parts of the stomach, but tachykinins also appear to inhibit motility in certain situations. Also, motility initiated centrally, mediated through the vagus nerves, is influenced by tachykinins. The precise role of tachykinin in the various motor programs in the stomach is not clear. Gastric acid secretion is influenced by tachykinins in several species. Tachykinins do not seem to act as neurotransmitters directly on parietal cells, but may have a modulatory function. The importance of tachykinins for the regulation of pepsinogen and hormone secretion from the stomach remains unclear. Received 24 August 1999; received after revision 1 December 1999; accepted 3 December 1999     

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.     

The performance of the octopus circulatory system: A triumph of engineering over design

Summary Despite the very considerable difficulties presented by the basic molluscan anatomy and the possession of a blood pigment with an oxygen carrying capacity that never exceeds 4.5 vols%, the cephalopod circulatory system contrives to deliver oxygen at a rate fully comparable with that of an active fish. This is achieved by adding accessory pumps to push blood through the gills, by a multiplicity of pulsatile veins and by raising the systemic blood pressure considerably above the levels found in other molluscs. Detailed control of blood distribution is a necessity in a system where the peripheral resistences may be expected to change dramatically when the animal starts to move and large parts of the central nervous system are apparently dedicated to this task. In this account we have reviewed blood pressure and flow at rest and in exercise. We have further examined the evidence which indicates how the animals modulate the cardiac output, drawing attention to the very different response found in cephalopods and the higher vertebrates.     

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.     

Two serotonin-sensitive potassium channels in the identified heart excitatory neurone of the African giant snail, Achatina fulica Fèrussac

By the patch clamp experiments, two serotonin-sensitive K+ channels (SL-channel and SS-channel) were demonstrated in the identified heart excitatory neurone (PON) of the African giant snail, Achatina fulica Fèrussac. The activities of both channels could be recorded in the steady state and those activities disappeared on application of 5-HT.     

Additional lectin receptors in galactans from the albumin gland of theAchatina fulica snail

Summary The lectin receptor-site specificity of a purified galactan from snail (Achatina fulica) albumin glands has been studied by precipitin reactions in agar-gel double diffusion experiments with different lectins. Most lectins were found to be specific for terminal -D-galactose structures. Some findings suggest, that the structure DGal13DGal may be one of the receptor sites on the polysaccharide.     

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.     

The Light Green Cells of Lymnaea: a neuroendocrine model system for stimulus-induced expression of multiple peptide genes in a single cell type.

We review recent experiments showing that the cerebral neuroendocrine Light Green Cells (LGCs) of the freshwater snail, Lymnaea stagnalis, express a family of distinct though related molluscan insulin-related peptide (MIP) genes. The LGCs are involved in the regulation of a wide range of interrelated life processes associated with growth, (energy) metabolism and reproduction. We consider the mechanism of generation of diversity among MIPs, and present evidence that conditions with distinct effects on growth, metabolism and reproduction also can induce distinct patterns of expression of the MIP and schistosomin genes. The stimulus-dependent expression of multiple neuropeptide genes enormously increases the adaptive potential of a peptidergic neuron. We suggest that this contributes significantly to the information-handling capacity of the brain.     

Modification of effects of biologically active peptides,caused by enzyme treatment,on the excitability of identifiable giant neurones of an African giant snail (Achatina fulica Férussac)

Summary Physalaemin, which excites an identifiable molluscan giant neurone (the TAN, tonically autoactive neurone), lost the effect after the trypsin treatment. Unexpectedly, this peptide shows an inhibitory effect on the same neurone after chymotrypsin treatment. Deamino-dicarba-(d-d-)oxytocin and d-d-Arg-vasotocin, which excite another identifiable neurone (the PON, periodically oscillating neurone) continue to show the effect after chymotrypsin treatment (6 h). But d-d-Arg-vasotocin losts the effect on the PON after trypsin treatment.The authors thank Dr Sadaaki Iwanaga of Osaka University and Dr Atsuo Inoue of Daiichi Pharmaceutical Co. for their helpful advice, and Miss Hiroko Tamura for her technical assistance.