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United States Department of Agriculture

Agricultural Research Service

Title: Diuretic and Myotropic Activities of N-Terminal Truncated Analogs of Musca Domestica Kinin Neuropeptide

Authors
item Coast, Geoffrey - BIRBECK COL. LONDON UK
item Zabrocki, Janusz - TECH UNIV OF LODZ POLAND
item Nachman, Ronald

Submitted to: Peptides
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: September 4, 2001
Publication Date: N/A

Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling such pests. The basic premise of this research is that peptides (short chains of amino acids) serve as potent internal messengers in insects to regulate vital functions Peptides themselves are unsuitable for control measures due to their instability to enzymes in the circulatory and digestive systems of the insect. New, selective control measures may be developed by designing metabolically stable mimics f these neuropeptides that actively inhibit or over-stimulate functions regulated by them, resulting in disruption of the internal environment of the insect. In this paper, we delineate the important chemical and structural features required for the diuretic activity of an insect kinin neuropeptide in the house fly, a pest of the poultry, swine, dairy, and confined beef industries. In addition to the so-called active core region (composed of 5 consecutive amino acids), full physiological activity requires the presence of three other amino acids in positions 2, 8 and 10 in this 15-membered neuropeptide. The work gives us a better understanding of how the neuropeptide works and provides clues to the development of potent mimics. This work leads us one step closer to the development of practical neuropeptide-like agents that will be effective in controlling certain pests in an environmentally friendly fashion.

Technical Abstract: Musca kinin (Musdo-K; NTVVLGKKQRFHSWG-NH2) and N-terminal truncated analogs of 4-14 residues in length were assayed for diuretic and myotropic activity on housefly Malpighian tubules and hindgut, respectively. The pentapeptide was the minimum sequence required for biological activity, but it was >5 orders of magnitude less potent than the intact peptide. The pharmacological profiles of the different analogs in the two assays were very similar, suggesting the same receptor is present on both tissues. Potency was little affected by the deletion of Asn1, but was reduced > 10-fold after the removal of Thr2. Deletion of the next 5 residues had relatively little effect, but after the second lysyl residue (Lys8) was removed potency fell by one to two orders of magnitude. There was a similar drop in potency after the removal of Arg10, and at 100 uM the pentapeptide had only 20% of the diuretic activity of the intact peptide. The importance of Arg10 was confirmed by comparing dose-response curves for Musdo-K[6-15] and Acheta kinin-V (AFSHWG-NH2) in the diuretic assay; the substitution of arginine by alanine produced a significant reduction in potency and some loss of activity.

Last Modified: 12/21/2014
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