Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FMRFamide”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

Neuromuscular function in plant parasitic nematodes: a target for novel control strategies?

Over the last decade the need for new strategies and compounds to control parasitic helminths has become increasingly urgent. The neuromuscular systems of these worms have been espoused as potential sources of target molecules for new drugs which may address this need. One facet of helminth neuromuscular biology which has garnered considerable research interest is that of neuropeptidergic neurotransmission, particularly regarding parasites of humans and animals, as well as free-living nematode model species. This research interest has been piqued by the fact that neuropeptides have been demonstrated to be fundamentally important to nematode biology and thus may be of utility in this search for new drug targets. This review focuses on the neuropeptide biology of plant parasitic nematodes, a subject which has been comparatively neglected despite the fact that the search for alternative control measures also extends to these economically important parasites. We focus on the FMRFamide-like peptide (FLP) neuropeptides and the complexity and distribution of this peptide family in plant parasitic nematodes. Possible roles for FLPs in plant parasitic nematode behaviour, as elucidated by a combination of molecular imaging techniques and RNA interference (RNAi), are discussed. We propose that disruption of FLP neurosignalling in plant parasitic nematodes represents a novel form of pest control and speculate as to how this may be achieved.

Animals↗

Modulation of the motility of the vagina vera of Ascaris suum in vitro by FMRF amide-related peptides.

Ascaris suum contains a large number of FMRFamide-related peptides (FaRPs) of which KNEFIRFamide (AF1), KHEYLRFamide (AF2) and KSAYMRFamide (AF8, also called PF3) have been extensively studied and are known to exert actions on somatic muscle strips of the worm. In the present study, the effects of AF1, AF2 and AF8 on the activity of the vagina vera of female A. suum have been examined in vitro. The vagina vera is a muscular tube connecting the uterus and vagina uteri to the gonopore and is probably involved in regulating egg output. The tissue exhibited spontaneous, rhythmic contractions in vitro, which were modulated by each of the FaRPs tested. The effects of each of the peptides were qualitatively and quantitatively different, and in each case were reversible. AF1 (1 microM) caused a biphasic response in the form of a transient lengthening of the preparation, followed by a shortening; contractions were initially inhibited but resumed 5 min post-addition of the peptide. Lower concentrations (< or = 0.1 microM) induced a less marked effect, with rhythmic contractions returning 5 min post-addition. AF2 and AF8 reduced contraction frequency at concentrations > or = 0.1 microM. Both peptides also caused the tissue to shorten, although the effects of AF8 on baseline tension were inconsistent. The apparent potencies of AF1 and AF8 on contraction frequency of the vagina vera were 10-fold greater than AF2 and, unlike their actions on A. suum somatic body wall muscles, the actions of AF1 and AF2 were qualitatively different. Indeed, the effects of each of these FaRPs on the vagina vera were markedly different from those observed on the somatic muscle.

Animals↗

Nematode neuropeptide modulation of the vagina vera of Ascaris suum: in vitro effects of PF1, PF2, PF4, AF3 and AF4.

Ascaris suum possesses a large number of FMRFamide-related peptides (FaRPs) of which KNEFIRFamide (AF1), KHEYLRFamide (AF2) and KSAYMRFamide (AF8/PF3) have been shown to modulate the intrinsic, rhythmic activity of the vagina vera of A. suum in vitro. In the present study, the effects of the nematode FaRPs, SDPNFLRFamide (PF1), SADPNFLREamide (PF2) and KPNFIRFamide (PF4) (from Panagrellus redivivus) and AVPGVLRFamide (AF3) and GDVPGVLRFamide (AF4) (from A. suum) on the in vitro activity of the vagina vera were examined. The effects of each of the peptides were qualitatively and quantitatively distinct. All 3 FaRPs from P. redivivus were inhibitory, causing a cessation of contractions. PF2 was 3 times more potent than PF1, with a threshold of 1 nM. Although PF4 was the least potent (threshold, 10 nM), its effects at > or = 10 nM were quantitatively the greatest. Both AF3 and AF4 (1 microM) induced complex, multiphasic responses consisting of an initial contraction and spastic paralysis followed by a return of contractile activity of increased amplitude. AF3 was 3 times more potent than AF4. The effects of these peptides had some similarities to those observed on A. suum somatic body wall muscle in vitro, with PF1, PF2 and PF4 being inhibitory and AF3 and AF4 being excitatory.

Animals↗

Partial characterization of a novel cardioinhibitory peptide from the brain of the snail Helix aspersa.

1. We report the isolation of a peptide from the brain of the snail Helix aspersa by radioimmunoassay using an antisomatostatin. 2. The sequencing of an immunopositive fraction showed the presence of a new tridecapeptide, termed Helix cardioinhibitory peptide (HCIP), with the following primary structure: H-Val-Phe-Gln-Asn-Gln-Phe-Lys-Gly-Ile-Gln-Gly-Arg-Phe-NH2. It is structurally related to the Achatina cardioexcitatory peptide (ACEP-1) and the terminal-amino acid sequence of HCIP is identical to that of FMRFamide family peptides. 3. The synthetic HCIP was tested on heart and neuronal activities and it was found to have inhibitory actions not only on the ventricle but also on visceral neurons of the central nervous system of Helix. Immunocytochemical investigation indicates its presence in visceral and parietal ganglia, in which cells taking part in the regulation of the heartbeat have been previously identified.

Amino Acid Sequence↗

On the synthesis of neurotransmitter receptor agonists with antagonist potential.

The synthesis of a new type of antagonist is described, capable of inactivating neuroreceptors with heretofore unattainable selectivity and permanence. These antagonists are referred to as mazek agonists (i.e. direct, inhibitory agonists) as they have the high receptor affinity and initial receptor-stimulatory effect of direct agonists and are positively coupled to effector systems. However, like direct antagonists, they have a high receptor affinity and the potential to inhibit or prevent receptor stimulation. The synthesis of the present compounds consisted of the covalent attachment of a tethered dye to three different neurotransmitter analogues, resulting in dye-neuropeptide conjugates with a high affinity for the FMRFa receptor. The dye was prepared from azure B (Az), the neurotransmitter was the neuropeptide FMRFamide (FMRFa), and the dye-neuropeptide conjugates synthesized were Az-CFMRFa; Az-CFMRF and Az-CLRFa. In this procedure, the analogues serve as carrier molecules, bound at one end to the receptor and at the other end to the dye, which is thereby brought into close contact with the receptor. The receptor can then be inactivated by singlet oxygen generated by laser irradiation of the photosensitized receptor.

Azure Stains↗

Centrifugal fibres synapse on dopaminergic interplexiform cells in the teleost retina.

In teleost fish, centrifugal fibres originating in the olfactory bulb and containing FMRFamide-like and luteinizing hormone releasing hormone (LHRH)-like peptides project to the retina and terminate along the border of the inner nuclear and inner plexiform layers. Using a novel simultaneous two-colour immunolabelling technique, we have found that these centrifugal fibres are often closely apposed to the dopaminergic interplexiform cells. Contacts between centrifugal fibres and dopaminergic interplexiform cells were observed by electron microscopy to be conventional type synaptic junctions. Since the dopaminergic interplexiform cells make synapses on horizontal and bipolar cells, providing an intraretinal centrifugal pathway for information flow from the inner to the outer plexiform layers, we conclude that every neuron in the teleost retina is potentially susceptible to central influences via these centrifugal fibres and dopaminergic interplexiform cells.

Animals↗

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-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 a 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.

Animals↗

Localization of myosuppressinlike peptides in the hypocerebral ganglion of two blood-feeding flies: horn fly and stable fly (Diptera:Muscidae).

The insect peptides leucomyosuppressin (pEDVDHVFLRFamide) and dromyosuppressin (TDVDHVFLRFamide) have identical chemical sequences with the exception of the N-terminal amino acid; both inhibit spontaneous contraction of insect visceral muscles. Neurons in the hypocerebral ganglion of horn fly, Hematobia irritans (L.), and stable fly, Stomoxys calcitrans (L.), were found to contain material immunoreactive to antiserum produced against the C-terminal of leucomyosuppressin, but not to the N-terminal of dromyossuppressin. Two large lateral clusters containing 8 cells, linked dorsally and ventrally by 2 chains of 6 cells, encircled the anterior surface of the proventriculus and were immunoreactive of leucomyosuppressin and FMRFamide antisera. Axons from these cells were traced to the wall of the aorta and over the surface of the proventriculus. Ultrastructural analysis revealed these cells contained a singular type of elementary secretory granule that contained material of relatively low electron density, both in the cell body and at the axon terminals.

Animals↗

flp gene disruption in a parasitic nematode reveals motor dysfunction and unusual neuronal sensitivity to RNA interference.

The potato cyst nematode Globodera pallida is a serious pest of potato crops. Nematode FMRFamide-like peptides (FLPs) are one of the most diverse neuropeptide families known, and modulate sensory and motor functions. As neuromuscular function is a well-established target for parasite control, parasitic nematode FLP signaling has significant potential in novel control strategies. In the absence of transgenic parasitic nematodes and the reported ineffectiveness of neuronal gene RNAi in Caenorhabditis elegans, nothing is known about flp function in nematode parasites. In attempts to evaluate flp function in G. pallida, we have discovered that, unlike in C. elegans, these genes are readily susceptible to RNAi. Silencing any of the five characterized G. pallida flp genes (Gp-flp-1, -6, -12, -14, or -18) incurred distinct aberrant behavioral phenotypes consistent with key roles in motor function. Further delineation of these effects revealed that double-stranded RNA exposure time (> or = 18 h) and concentration (> or = 0.1 microg/ml) were critical to the observed effects, which were reversible. G. pallida flp genes are essential to coordinated locomotory activities, do not display redundancy, and are susceptible to RNAi, paving the way for the investigation of RNAi-mediated flp gene silencing as a novel plant parasite control strategy.

Animals↗

Defective processing of neuropeptide precursors in Caenorhabditis elegans lacking proprotein convertase 2 (KPC-2/EGL-3): mutant analysis by mass spectrometry.

Biologically active peptides are synthesized as larger inactive proprotein peptide precursors which are processed by the concerted action of a cascade of enzymes. Among the proprotein convertases, PC2 is widely expressed in neuro-endocrine tissues and has been proposed to be the major convertase involved in the biosynthesis of neuropeptides. In this study, we have examined the role of the Caenorhabditis elegans orthologue PC2/EGL-3 in the processing of proprotein peptide precursors. We recently isolated and identified 60 endogenous peptides in the nematode C. elegans by two-dimensional nanoscale liquid chromatography - quadrupole time-of-flight tandem mass spectrometry. In the present study, we compare the peptide profile of different C. elegans strains, including PC2/EGL-3 mutants. For this purpose, we used an offline approach in which HPLC fractions are analysed by a matrix-assisted laser desorption ionisation - time of flight mass spectrometer. This differential peptidomic approach unambiguously provides evidence for the role of PC2/EGL-3 in the processing of FMRFamide-like peptide (FLP) precursors and neuropeptide-like protein (NLP) precursors in nematodes.

Animals↗

Effects of acetylcholine on a slow voltage-activated non-selective cation current mediated by non-nicotinic receptors on isolated Ascaris muscle bags.

Isolated muscle bags from the parasitic nematode Ascaris suum were prepared by collagenase treatment and dissection. Single bags were mounted in a V-shaped plastic pipette for voltage clamp application and intra- and extracellular perfusion. With 'physiological' intra- and extracellular solutions, depolarizing voltage steps from near the normal resting membrane potential, -40 mV, produced in leak-corrected currents, a slowly activating outward current at potentials more positive than -20mV. At the end of the depolarizing pulse there was a slow inward tail current with a reversal potential near -20mV. Hyperpolarizing voltage steps produced an outward current relaxation and an outward tail current with the same reversal potential. The observations can be explained by the presence in the bag of a non-selective cation channel current, Ibcat, that activates spontaneously at the holding potential; depolarization increases opening of the channel and hyperpolarization decreases opening. Bath-applied acetylcholine in concentrations greater than 10(-7) M produced an increase in the amplitude of Ibcat. The effect of acetylcholine was not antagonized or prevented by 100 microM tubocurarine, suggesting the presence of a non-nicotinic acetylcholine receptor. Atropine (100 microM) had no detectable influence on the effect of acetylcholine but the FMRFamide peptide, PF1, in concentrations > 1 microM, reduced the amplitude of Ibcat. Ibcat was maintained when Cs+ was used to replace intra- and extracellular cations, showing that the channels were permeable to Cs+. It is concluded that the bag membrane possesses a slow voltage-activated non-selective cation channel current, Ibcat. The effect of acetylcholine in the presence of nicotinic antagonist indicates the presence of non-nicotinic acetylcholine receptors on the bag membrane. The effect of PF1 indicated the presence of PF1 receptors on the bag membrane.

Acetylcholine↗

Multiple actions of a molluscan cardioexcitatory neuropeptide and related peptides on identified Helix neurones.

The effects of the molluscan neuropeptide Phe-Met-Arg-Phe-NH2 (FMRF amide) and related peptides (Price & Greenberg, 1977) were tested on Helix aspersa neurones. Ionophoretic application of FMRFamide depolarized and excited some neurones, but hyperpolarized and inhibited others. In some neurones the sign of the response was dependent on the membrane potential. Two responses resulted from an increase in membrane conductance, a depolarizing response mediated mainly by an increase in Na+ ion permeability, and a hyperpolarizing response mediated by an increase in K+ ion permeability. In the C1 neurone a voltage-dependent response was observed, which only occurred when the neurone was depolarized from its resting level. This response was recorded as an inward current during voltage clamp and resulted from a decrease in K current(s), possibly Ca-activated K current. More than one response may occur in a single neurone. In the C1 neurone, the K-mediated hyperpolarization occurred as well as the voltage-dependent response, while the depolarization seen in the F2 neurone was a combination of an increase in Na conductance and an increase in K conductance.

Animals↗

The effects of small cardioactive peptide B on the isolated heart and gill of Aplysia californica.

Effects of small cardioactive peptide B on the physiology of the isolated heart and gill preparations from the mollusc Aplysia californica were examined. In addition, the effects of small cardioactive peptide B and FMRFamide (Phe-Met-Arg-Phe-NH2) on adenylate cyclase activity were compared in particulate fractions of heart and gill tissues, respectively. Small cardioactive peptide B was found to exert dose-dependent, reversible changes in cardiac activity when perfused through the isolated heart. The EC50 values effecting changes in heart rate and force of contraction were 3 X 10(-11) and 3 X 10(-10) M, respectively; minimum concentrations found to effect changes in heart rate and force of contraction were normally 10(-15) and 10(-12) M, respectively. However, some winter hearts demonstrated threshold sensitivity to small cardioactive peptide B at concentrations as low as 10(-17) M. When perfused through the isolated gill, small cardioactive peptide B was found to suppress the gill withdrawal response amplitude with a threshold concentration of 10(-14) M and an EC50 value of 3 X 10(-11) M. Suppression of the gill withdrawal response amplitude by small cardioactive peptide B was found to be dose dependent and reversible up to a concentration of 10(-9) M. At higher concentrations, the suppression tended to persist irreversibly. Small cardioactive peptide B stimulated adenylate cyclase activity in particulate fractions of both heart and gill tissues with an EC50 of 0.1 and 1.0 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

FRF peptides in the ARC neuromuscular system of Aplysia: purification and physiological actions.

1. One preparation that has proven to be advantageous for the study of neuromuscular modulation is the accessory radula closer (ARC) muscle of Aplysia californica and its motor neurons B15 and B16. In this study three members of a new peptide family have been purified from this well-characterized preparation. Because these peptides terminate in Phe-Arg-Phe-amide, we have named them FRFA, FRFB, and FRFC. The FRFs are thus RFamide peptides and are related to the widely studied neuropeptide FMRFamide. 2. The FRFs are present in the ARC motor neuron B15 in small quantities. 3. When they are exogenously applied, the FRFs decrease the size of ARC muscle contractions elicited by stimulation of either motor neuron B15 or B16. They appear to do this by a combination of presynaptic and postsynaptic actions. 4. Presynaptically, the FRFs appear to act like the buccalins, another family of inhibitory ARC neuropeptides. Both families of peptides reduce the size of motor neuron-elicited excitatory junction potentials (EJPs) presumably by decreasing presynaptic acetylcholine (ACh) release. 5. Postsynaptically, the FRFs appear to depress contractions because they activate a characteristic voltage-dependent, 4-amino-pyridine-sensitive K current in the ARC muscle. The same current is activated by a second class of ARC modulators: those that exert potentiating actions at low doses and inhibitory actions at high doses, i.e., serotonin, the small cardioactive peptides (SCPs), and particularly the myomodulins. Receptors mediating activation of the K current by the FRFs and the other modulators do, however, appear to be different. 6. We hypothesize that the inhibitory actions of the FRFs prevent excessively large muscle contractions. If contraction size is limited, then contraction duration is also limited. This may allow faster and more energetically favorable switching between contractions of antagonistic muscles.

Acetylcholine↗

Ion currents and mechanisms of modulation in the radula opener muscles of Aplysia.

Ion currents and mechanisms of modulation in the radula opener muscles of Aplysia. J. Neurophysiol. 78: 2372-2387, 1997. Numerous studies of plasticity in the feeding behavior of Aplysia have shown that substantial plasticity is due to peripheral neuromodulation of the feeding musculature. Extensive previous work focusing on the accessory radula closer (ARC) muscle has led to the realization that a major function of the modulation in that muscle may be to ensure efficient coordination between its contractions and those of its antagonist muscles. For a more complete understanding, therefore, we must study these muscles also. Here we have studied the radula opener muscles I7-I10. Using single isolated muscle fibers under voltage clamp, we have characterized ion currents gated by voltage and by the physiological contraction-inducing neurotransmitter acetylcholine (ACh) and the effects of the physiological modulators serotonin, myomodulins A and B, and FMRFamide. Our results explain significant aspects of the electrophysiological behavior of the whole opener muscles, as well as why the opener and ARC muscles behave similarly in many ways yet differently in some key respects. Opener muscles express four types of K currents: inward rectifier, A-type [IK(A)], delayed rectifier [IK(V)], and Ca2+-activated [IK(Ca)]. They also express an L-type Ca current [ICa] and a leakage current. ACh activates a positive-reversing cationic current [IACh(cat)] and a negative-reversing Cl current [IACh(Cl)]. The opener muscles differ from the ARC in that, in the openers, activation of IK(A) occurs approximately 9 mV more positive and there is much less IACh(Cl). In both muscles, IACh(cat) most likely serves to depolarize the muscle until ICa activates to supply Ca2+ for contraction, but further depolarization and spiking is opposed by coactivation of IK(A), IK(V), IK(Ca), and IACh(Cl). Thus the differences in IK(A) and IACh(Cl) may well be key factors that prevent spikes in the ARC but often allow them in the opener muscles. As in the ARC, the modulators enhance ICa and so potentiate contractions. They also activate a modulator-specific K current, which causes hyperpolarization and depression of contractions. Finally, in the opener muscles but not in the ARC, the modulators activate a depolarizing cationic current that may help phase-advance the contractions. Each modulator exerts these effects to different degrees and thus has a distinct effect on voltage and contraction size and shape. The overall effect then will depend on the specific combinations of modulators released in different behaviors. By understanding the modulation in the opener muscles, as well as in the ARC, we are now in a position to understand how the behavior of the two muscles is coordinated under a variety of circumstances.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Protein kinase C is required for long-lasting synaptic enhancement by the neuropeptide DRNFLRFamide in crayfish.

The FMRFamide-related neuropeptide AspArgAsnPheLeuArgPhe-NH2 (DRNFLRFamide, DF2) induces a long-lasting enhancement of synaptic transmission at neuromuscular junctions on the crayfish deep abdominal extensor muscles. Here we investigated the function of protein kinase C (PKC) in this effect because PKC has been implied in the control of long-term synaptic modulation in other systems. The general kinase antagonist staurosporine reduced both the initial increase in excitatory postsynaptic potential (EPSP) amplitude and the duration of synaptic enhancement. Unlike staurosporine, the selective PKC inhibitors, chelerythrine and bisindolylmaleimide, augmented the initial EPSP increase. However, like staurosporine, they also reduced the duration of synaptic enhancement. The PKC activator, phorbol-12-myristate 13-acetate, induced a long-lasting synaptic enhancement that was blocked by chelerythrine. These results show that synaptic enhancement by DF2 is mediated by different intracellular signaling systems that act in temporal sequence. The initial increase in EPSP amplitudes is negatively regulated by PKC and involves another, staurosporine-sensitive, kinase; whereas, the maintenance of synaptic enhancement requires PKC.

Alkaloids↗

Evidence that post-tetanic potentiation is mediated by neuropeptide release in Aplysia.

Many neuromuscular and central synapses exhibit activity-dependent plasticity. The sustained high-frequency firing needed to elicit some forms of plasticity are similar to those often required to release neuropeptides. We wanted to determine if neuropeptide release could contribute to post-tetanic potentiation (PTP) and chose neuromuscular synapses in buccal muscle I3a to explore this issue. This muscle is innervated by two motor neurons (termed B3 and B38) that show PTP in response to tetanic stimulation. B3 and B38 use glutamate as their fast transmitter but express different modulatory neuropeptides. B3 expresses FMRFamide, a neuropeptide that only slightly increases its own excitatory junction potentials (EJPs). B38 expresses the small cardioactive peptide (SCP), a neuropeptide that dramatically increases its own EJPs. It was our hypothesis that SCP released from B38's terminals during tetanic stimulation mediated a component of PTP for B38. Because no antagonist to SCP currently exists, we used several indirect approaches to test this hypothesis. First, we studied the effects of increasing stimulation frequency during the tetanus or lowering temperature on PTP. Both of these changes are known to dramatically increase SCP release. We found that increasing the frequency of stimulation increased PTP for both neurons; however, the effects were larger for B38. Decreasing the temperature tended to reduce PTP for B3, while increasing PTP for B38. These results were consistent with known properties of SCP release from B38. Next we selectively superfused the neuromuscular synapses with exogenous SCP to determine if this would occlude the effects of SCP released from B38 during a tetanus. We found that exogenous SCP dramatically reduced PTP for B38 but had little effect on PTP for B3. Thus our results support the hypothesis that physiological stimulation of B38 elicits PTP that is predominantly dependent on the release of SCP from its own terminals. They also demonstrate that the mechanisms underlying PTP can be very different for two motor neurons innervating the same target muscle.

Animals↗