A role for cyclic nucleotide monophosphates in synaptic modulation by a crayfish neuropeptide.
DF2 (DRNFLRFamide), a FMRFamide-like peptide, has been shown to increase the amount of transmitter released at crayfish neuromuscular junctions. Here, we examined a possible role for the cyclic nucleotide monophosphates, cAMP and cGMP, in DF2's effects on synaptic transmission. The effects of DF2 on synaptic transmission were monitored by recording excitatory postsynaptic potentials (EPSPs) in the deep abdominal extensor muscles of the crayfish, Procambarus clarkii. A number of activators and inhibitors were used to determine whether or not cAMP, cGMP, protein kinase A (PKA) and protein kinase G (PKG) mediate the effect of this neuropeptide. Phosphodiesterase inhibitors, known to inhibit the breakdown of cAMP (IBMX) and/or cGMP (mdBAMQ), potentiate the effect of DF2 on synaptic transmission. Activators of PKA (Sp-cAMPS) and PKG (8-pCPT-cGMP) increase EPSP amplitude, mimicking the effects of DF2. Inhibitors of PKA (Rp-cAMPS) and PKG (Rp-8-pCPT-cGMPS) each block a portion of the response to the peptide, and when applied together these two inhibitors completely block the response. Taken together, these results indicate that cyclic nucleotides and cyclic nucleotide-dependent protein kinases are necessary components of the pathway underlying modulation by this neuropeptide.
Badhwar
Amit
A
Department of Biological Sciences, Brock University, St. Catharines, Ont., Canada L2S 3A1.
Weston
Andrea D
AD
Murray
Jillian B
JB
Mercier
A Joffre
AJ
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D003400:Astacoidea; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000494:pharmacology; D009479:Neuropeptides / Q000737:chemistry*; D009711:Nucleotides / Q000737:chemistry; D009712:Nucleotides, Cyclic / Q000737:chemistry / Q000502:physiology*; D010455:Peptides / Q000737:chemistry; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission; D013873:Thionucleotides / Q000737:chemistry* / Q000494:pharmacology
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D009479:Neuropeptides; D009711:Nucleotides; D009712:Nucleotides, Cyclic; D010455:Peptides; D013873:Thionucleotides; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine