|Nachman, Ronald - Ron|
Submitted to: Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/19/2008
Publication Date: 9/15/2008
Citation: Paluzzi, J., Russell, W.K., Nachman, R.J., Orchard, I. 2008. Isolation, cloning and expression mapping of a gene encoding an anti-diuretic hormone and other CAPA-related peptides in the disease vector, Rhodnius prolixus. Endocrinology. 149:4638-4646. 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 insect pests. The basic premise of this research is that neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that actively inhibit or over-stimulate functions regulated by them, resulting in disruption of the internal environment of the insect. We report on the sequence of a major gene, which reveals the identity of a neuropeptide that has ‘anti-diuretic’ activity in the assassin bug, a vector for Chagas disease that afflicts humans. The ‘anti-diuretic’ activity inhibits the urine production that is responsible for transmission of the causative agent of Chagas disease. The above results suggest that development of metabolically stable versions of this neuropeptide could lead to agents capable of disrupting water balance and disease transmission in this insect, as well as other insects that pose as threats to human health and agriculture. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest insects in an environmentally friendly fashion.
Technical Abstract: Following a blood meal, Rhodnius prolixus undergoes a rapid diuresis in order to eliminate excess water and salts. During the voiding of this primary urine, R. prolixus acts as a vector of Chagas’ disease, with the causative agent, Trypanosoma cruzi, infecting the human host via the urine. Diuresis in R. prolixus is under the neurohormonal control of serotonin and peptidergic diuretic hormones, and thus diuretic hormones play an important role in the transmission of Chagas’ disease. Although diuretic hormones may be degraded or excreted resulting in the termination of diuresis, it would also seem appropriate, given the high rates of secretion, that a potent anti-diuretic factor could be present and act to prevent excessive loss of water and salts following the post-gorging diuresis. Despite the medical importance of R. prolixus, no genes for any neuropeptides have been cloned, including obviously, those that control diuresis. Here, using molecular biology in combination with MALDI-TOF/TOF tandem mass spectrometry, we have determined the sequence of the CAPA gene and CAPA-related peptides in R. prolixus, which includes a peptide with anti-diuretic activity. We have characterized the expression of mRNA encoding these peptides in various developmental stages and have also examined the tissue-specific distribution in fifth-instars. The expression is localized to numerous bi-laterally paired cell bodies within the central nervous system. In addition, our results show that RhoprCAPA gene expression is also associated with the testes, suggesting a novel role for this family of peptides in reproduction.