ATP analogues and other phosphate compounds as gorging stimulants for Rhodnius prolixus

Abstract

Five analogues of ATP and six other non-nucleotide compounds with phosphate groups were tested as gorging stimulants for second-instar larvae of Rhodnius prolixus to determine the importance of the phosphate chain. Only molecules with terminal phosphate groups were potent. Insertion of an imido group (5′-Adenylylimidodiphosphate, AMP-PNP) or a methylene group (β, γ-Methylene adenosine 5′-triphosphate, AMP-PCP) between the β and γ phosphates of ATP reduced the potency compared to ATP by ratios of 1.8 and 25.5, respectively. Substituting ribose (Adenosine 5′-diphosphoribose, AMP-PR) for the γ phosphate group or an amidate or a sulphate group (Adenosine 5′-phosphoramidate, AMP-N; Adenosine 5′-phosphosulphate, AMP-S) for the β and γ phosphate groups of ATP resulted in a complete loss of stimulatory activity. Some non-nucleotide phosphate compounds were potent phagostimulants. Pyrophosphate with an ED 50 of 64 μM had a potency ratio compared with ATP of 1:17. Methylene diphosphonic acid (ED 50 680 μM) and even single phosphate ions (ED 50 2.5 mM) had substantial potency. Two isomers of phosphoglyceric acid differ greatly in their ability to stimulate gorging; 2-PGA was active (ED 50 160 μM) whereas 3-PGA had almost no activity. A summary of known phagostimulants to R. prolixus supports the hypothesis that ATP-like gorging stimulants act by forming a temporary binding to 3 sites on a receptor protein in the membrane of the chemosensory cell. The amino group on C 6 of adenine, the OH group on C 2 of ribose and the terminal phosphate group(s) determine potency, presumably by determining binding affinity. However, only the phosphate group appears essential to the chemosensory process.