Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous peptides are structurally related to the cardioexcitatory tetrapeptide FMRFamide. One subgroup of FMRFamide-related peptides (FaRPs) contains an FMRFamide C terminus. Searches of the Drosophila melanogaster genome database identified the first invertebrate FMRFamide G-protein coupled receptor (GPCR), DrmFMRFa-R (Cazzamali and Grimmelikhuijzen, Meeusen et al., 2002). In order to explore molecular mechanisms involved in FMRFamide signal transduction we identified a receptor from the malaria mosquito Anopheles gambiae genome (Holt et al., 2002), AngFMRFa-R, and compared its structure to DrmFMRFa-R. The cytoplasmic loops, extracellular loops, and transmembrane regions are highly conserved between these two FMRFamide receptors. Another subgroup of FaRPs is the sulfakinins which are represented by the consensus structure -XDYGHMRFamide, where X is D or E (Nichols, 2003). We compared AngFMRFa-R and DrmFMRFa-R to the A. gambiae sulfakinin receptors, ASK-R1 and ASK-R2 ( Duttlinger et al., 2003), and the D. melanogaster sulfakinin receptors, DSK-R1 and DSK-R2 Brody and Cravchik, 2000; Hewes and Taghert, 2001 ). The cytoplasmic loops, extracellular loops, and the transmembrane regions are not highly conserved between the FMRFamide and sulfakinin receptors. In order to explore the role of FMRFamide in mosquito biology we measured the effect of the tetrapeptide on in vivo heart rate. The tetrapeptide increased the frequency of spontaneous contractions of the larval mosquito heart and, thus, increased heart rate. These data support the conclusion that the structure of the FMRFamide receptor and activity of the cardioexcitatory FMRFamide neuropeptide are conserved in mosquito.
 ...
PMID:The structure of the FMRFamide receptor and activity of the cardioexcitatory neuropeptide are conserved in mosquito. 1274 44

The insect myosuppressins (X1DVX2HX3FLRFamide) are neuropeptides that generally block insect muscle activities. We have used the genomic sequence information from the malaria mosquito Anopheles gambiae Genome Project to clone a G protein-coupled receptor that was closely related to the two previously cloned and characterized myosuppressin receptors from Drosophila [Proc. Natl. Acad. Sci. USA 100 (2003) 9808]. The mosquito receptor cDNA was expressed in Chinese hamster ovary cells and was found to be activated by low concentrations of Anopheles myosuppressin (TDVDHVFLRFamide; EC50, 1.6 x 10(-8)M). The receptor was not activated by a library of 35 other insect neuropeptides and monoamines, including neuropeptides that resembled myosuppressin in their C-terminal moiety, such as PDRNFLRFamide (Anopheles FMRFamide-3), other Anopheles FMRFamide peptides, or neuropeptide F-like peptides, showing that the receptor was quite selective for myosuppressin. These results also showed that the myosuppressin receptor needs a much larger portion than the C-terminal FLRFamide sequence for its activation. The insect myosuppressins are often grouped together with the insect FMRFamides under the name FaRPs (FMRFamide-related peptides). However, this is not justified anymore, because the insect myosuppressin receptor/ligand couple is both functionally and evolutionarily fully unrelated to the insect FMRFamide receptor/ligand couple. To our knowledge, this is the first report on the molecular identification of a mosquito neuropeptide receptor.
 ...
PMID:Molecular identification of a myosuppressin receptor from the malaria mosquito Anopheles gambiae. 1562 25