Effects of KHEYLRFamide and KNEFIRFamide on cyclic adenosine monophosphate levels in Ascaris suum somatic muscle

Thompson, David P.; Davis, John P.; Larsen, Martha J.; Coscarelli, E.M.; Zinser, Erich W.; Bowman, J.W.; Alexander-Bowman, Susan J.; Marks, Nikki J.; Geary, Timothy G.

doi:10.1016/s0020-7519(02)00259-x

Cited by 19 publications

(11 citation statements)

References 36 publications

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“…Control injected worms did not show a significant change in body length (Table 2). Basal levels of cAMP and cGMP were in good agreement with the values reported in A. suum by Thompson et al [36]…”

Section: Resultssupporting

confidence: 90%

“…In contrast, AF2 dramatically increased cAMP, by 175-fold, but had no effect on cGMP levels. Thompson et al [36] have confirmed our results on the effects of AF1 and AF2 on cAMP levels, but did not observe any effect of AF1 on cGMP levels.…”

Section: Resultssupporting

confidence: 89%

“…In almost all cases the three techniques give the same answer. The other half of the cellular signaling dyad, namely the cells bearing the receptors for each peptide, has been explored by observing peptide effects on the electrophysiological properties of single neurons [9, 24], on muscle cells [7, 8, 25–27, 29, 33–35], and on levels of cAMP [28, 36]. …”

Section: Introductionmentioning

confidence: 99%

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Changes in cyclic nucleotides, locomotory behavior, and body length produced by novel endogenous neuropeptides in the parasitic nematode Ascaris suum

Reinitz¹,

Pleva²,

Stretton³

2011

Molecular and Biochemical Parasitology

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Recent technical advances have rapidly advanced the discovery of novel peptides, as well as the transcripts that encode them, in the parasitic nematode Ascaris suum. Here we report that many of these novel peptides produce profound and varied effects on locomotory behavior and levels of cyclic nucleotides in A. suum. We investigated the effects of 31 endogenous neuropeptides encoded by transcripts afp-1, afp-2, afp-4, afp-6, afp-7, and afp-9 - 14, (afp: Ascaris FMRFamide –like Precursor protein) on cyclic nucleotide levels, body length and locomotory behavior. Worms were induced to generate anteriorly propagating waveforms, peptides were injected into the pseudocoelomic cavity, and changes in the specific activity (nmol/mg protein) of second messengers cAMP (3′5′ cyclic adenosine monophosphate) and cGMP (3′5′ cyclic guanosine monophosphate) were determined. Many of these neuropeptides changed the levels of cAMP (both increases and decreases were found), whereas few neuropeptides changed the level of cGMP. A subset of the peptides that lowered cAMP was investigated for effects on the locomotory waveform and on body length. Injection of AF19, or AF34 (afp-13), AF9 (afp-14), AF26 or AF41 (afp-11) caused immediate paralysis and cessation of propagating body waveforms. These neuropeptides also significantly increased body length. In contrast, injection of AF15 (afp-9) reduced the body length, and decreased the amplitude of waves in the body waveform. AF30 (afp-10) produced worms with tight ventral coils. Although injection of neuropeptides encoded by afp-1 (AF3, AF4, AF10 or AF13) produced an increased number of exaggerated body waves, there were no effects on either cAMP or cGMP. By injecting peptides into behaving A. suum, we have provided an initial screen of the effects of novel peptides on several behavioral and biochemical parameters.

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Section: Resultssupporting

confidence: 90%

Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Changes in cyclic nucleotides, locomotory behavior, and body length produced by novel endogenous neuropeptides in the parasitic nematode Ascaris suum

Reinitz¹,

Pleva²,

Stretton³

2011

Molecular and Biochemical Parasitology

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“…Since raised levels of cAMP enhance the excitatory effect of FLP17A it would appear that at least a component of this excitation is modulated through a cAMP-dependent process. This is supported by earlier studies using A. suum body wall muscle which suggested that FLPs, including those identified in C. elegans, can alter the level of muscle cAMP (Reinitz et al 2000;Thompson et al 2003).…”

Section: Discussionsupporting

confidence: 74%

Evidence for a role for cyclic AMP in modulating the action of 5-HT and an excitatory neuropeptide, FLP17A, in the pharyngeal muscle of Caenorhabditis elegans

2008

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The feeding activity of the nematode Caenorhabditis elegans is regulated by an anatomically well-defined network of 20 enteric neurones that employs small molecule and neuropeptidergic signalling. Two of the most potent excitatory agents are 5-HT and the neuropeptide FLP17A. Here we have examined the role of cAMP in modulating their excitatory actions by pharmacological manipulation of the level of cAMP. Application of the membrane permeable cAMP analogue, dibutyryl-cAMP (1 microM), enhanced the excitatory response to both FLP17A and 5-HT. Furthermore, the adenylyl cyclase activator, forskolin (50 nM), significantly enhanced the excitatory response to both FLP17A and 5-HT. The phosphodiesterase inhibitor, ibudilast (10 microM), enhanced the excitatory response to FLP17A. The protein kinase inhibitor, H-9 dihydrochloride (10 microM) significantly reduced the excitatory response to 5-HT. H-9 dihydrochloride also had a direct effect on pharyngeal activity. The effect of FLP17A and 5-HT on two mutants, egl-8 (loss-of-function phospholipase-Cbeta) and egl-30 (loss-of-function Galphaq) was also investigated. Both these mutants have a lower pharyngeal pumping rate than wild-type which has to be considered when interpreting the effects of these mutations on the excitatory responses to FLP17A and 5HT. However, even taking into consideration the lower basal activity of these mutants, it is clear that the percentage increase in pharyngeal pumping rate induced by FLP17A is greatly reduced in both mutants compared to wild-type. In the case of 5-HT, the effect of the mutant backgrounds on the response was less pronounced. Overall, the data support a role for cAMP in modulating the excitatory action of both FLP17A and 5-HT on C. elegans pharyngeal pumping and furthermore implicate an EGL-30 dependent pathway in the regulation of the response to FLP17A.

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“…Although an array of FLP peptides clearly shows muscle-based effects, denervation of somatic muscle strips can alter or even abolish the activity of many FLPs indicating that FLP-receptors do not only reside on muscles (1, 92). Electrophysiological studies indeed demonstrate that FLPs, such as AF1, can act through modulation of neuronal conductance of motor neurons in addition to their muscle-based effects (137). Contrary to AF1, the effects of AF8 (KSAYMRFa) on somatic muscle of A. suum are uniquely differential and context-dependent.…”

Section: Flp-mediated Modulation Of Nematode Physiology and Behaviormentioning

confidence: 99%

The FMRFamide-Like Peptide Family in Nematodes

et al. 2014

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In the three decades since the FMRFamide peptide was isolated from the mollusk Macrocallista nimbosa, structurally similar peptides sharing a C-terminal RFamide motif have been identified across the animal kingdom. FMRFamide-like peptides (FLPs) represent the largest known family of neuropeptides in invertebrates. In the phylum Nematoda, at least 32 flp-genes are classified, making the FLP system of nematodes unusually complex. The diversity of the nematode FLP complement is most extensively mapped in Caenorhabditis elegans, where over 70 FLPs have been predicted. FLPs have shown to be expressed in the majority of the 302 C. elegans neurons including interneurons, sensory neurons, and motor neurons. The vast expression of FLPs is reflected in the broad functional repertoire of nematode FLP signaling, including neuroendocrine and neuromodulatory effects on locomotory activity, reproduction, feeding, and behavior. In contrast to the many identified nematode FLPs, only few peptides have been assigned a receptor and there is the need to clarify the pathway components and working mechanisms of the FLP signaling network. Here, we review the diversity, distribution, and functions of FLPs in nematodes.

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Effects of KHEYLRFamide and KNEFIRFamide on cyclic adenosine monophosphate levels in Ascaris suum somatic muscle

Cited by 19 publications

References 36 publications

Changes in cyclic nucleotides, locomotory behavior, and body length produced by novel endogenous neuropeptides in the parasitic nematode Ascaris suum

Changes in cyclic nucleotides, locomotory behavior, and body length produced by novel endogenous neuropeptides in the parasitic nematode Ascaris suum

Evidence for a role for cyclic AMP in modulating the action of 5-HT and an excitatory neuropeptide, FLP17A, in the pharyngeal muscle of Caenorhabditis elegans

The FMRFamide-Like Peptide Family in Nematodes

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