Autor(es): Okech, Bernard A.; Boudko, Dmitri Y.; Linser, Paul J.; Harvey, William R.

Resumo: Anopheles gambiae larvae (DIPTERA: Culicidae) live in freshwater with low Na super(+) concentrations yet they use Na super(+) for alkalinization of the alimentary canal, for electrophoretic amino acid uptake and for nerve function. The metabolic pathway by which larvae accomplish these functions has anionic and cationic components that interact and allow the larva to conserve Na super(+) while excreting H super(+) and HCO sub(3) super(-). The anionic pathway consists of a metabolic CO sub(2) diffusion process, carbonic anhydrase and Cl super(-)/HCO sub(3) super(-) exchangers; it provides weak HCO sub(3) super(-) and weaker CO sub(3) super(2-) anions to the lumen. The cationic pathway consists of H super(+) V-ATPases and Na super(+)/H super(+) antiporters (NHAs), Na super(+)/K super(+) P-ATPases and Na super(+)/H super(+) exchangers (NHEs) along with several (Na super(+) or K super(+)):amino acid super(+/-) symporters, a.k.a. nutrient amino acid transporters (NATs). This paper considers the cationic pathway, which provides the strong Na super(+) or K super(+) cations that alkalinize the lumen in anterior midgut then removes them and restores a lower pH in posterior midgut. A key member of the cationic pathway is a Na super(+)/H super(+) antiporter, which was cloned recently from Anopheles gambiae larvae, localized strategically in plasma membranes of the alimentary canal and named AgNHA1 based upon its phylogeny. A phylogenetic comparison of all cloned NHAs and NHEs revealed that AgNHA1 is the first metazoan NHA to be cloned and localized and that it is in the same clade as electrophoretic prokaryotic NHAs that are driven by the electrogenic H super(+) F-ATPase. Like prokaryotic NHAs, AgNHA1 is thought to be electrophoretic and to be driven by the electrogenic H super(+) V-ATPase. Both AgNHA1 and alkalophilic bacterial NHAs face highly alkaline environments; to alkalinize the larva mosquito midgut lumen, AgNHA1, like the bacterial NHAs, would have to move nH super(+) inwardly and Na super(+) outwardly. Perhaps the alkaline environment that led to the evolution of electrophoretic prokaryotic NHAs also led to the evolution of an electrophoretic AgNHA1 in mosquito larvae. In support of this hypothesis, antibodies to both AgNHA1 and H super(+) V-ATPase label the same membranes in An. gambiae larvae. The localization of H super(+) V-ATPase together with (Na super(+) or K super(+)):amino acid super(+/-) symporter, AgNAT8, on the same apical membrane in posterior midgut cells constitutes the functional equivalent of an NHE that lowers the pH in the posterior midgut lumen. All NATs characterized to date are Na super(+) or K super(+) symporters so the deduction is likely to have wide application. The deduced colocalization of H super(+) V-ATPase, AgNHA1 and AgNAT8, on this membrane forms a pathway for local cycling of H super(+) and Na super(+) in posterior midgut. The local H super(+) cycle would prevent unchecked acidification of the lumen while the local Na super(+) cycle would regulate pH and support Na super(+):amino acid super(+/-) symport. Meanwhile, a long-range Na super(+) cycle first transfers Na super(+) from the blood to gastric caeca and anterior midgut lumen where it initiates alkalinization and then returns Na super(+) from the rectal lumen to the blood, where it prevents loss of Na super(+) during H super(+) and HCO sub(3) super(-) excretion. The localization of H super(+) V-ATPase and Na super(+)/K super(+)-ATPase in An. gambiae larvae parallels that reported for Aedes aegypti larvae. The deduced colocalization of the two ATPases along with NHA and NAT in the alimentary canal constitutes a cationic pathway for Na super(+)-conserving midgut alkalinization and de-alkalinization which has never been reported before.

Palavras-Chave: Public health; Rectum; Anions; F-ATPase; Nutrients; Carbonate dehydratase; Chloride; Phylogeny; Amino acids; Adenosinetriphosphatase; Freshwater environments; Excretion; Carbon dioxide; Evolution; Aedes aegypti; Culicidae; Metazoa; Diptera; Anopheles gambiae

Imprenta: Journal of Experimental Biology, v. 211, n. 6, p. 957-968, 2008.

Descritores: Aedes aegypti - Cell ; Aedes aegypti - Public health

Data de publicação: 2008