The effect of analogues of adipokinetic hormone II on second messenger systems in the fat body of Schistocerca gregaria

Analogues of the locust adipokinetic hormone-2 from Schistocerca gregaria were tested for their ability to stimulate two signalling pathways in the locust fat body. A series of analogues in which successive amino acids were replaced by alanine was synthesized and their ability to stimulate the turnover of 3H-labelled inositol trisphosphates and the accumulation of cyclic AMP in vitro was investigated. Unmodified adipokinetic hormone-2 stimulated both pathways, but substitution of phenylalanine at position 4 or tryptophan at position 8 by alanine, produced peptides that were unable to stimulate either signalling pathway. Dose response curves are presented for the increase in inositol phosphates that occurred when fat body tissue was stimulated with the remaining analogues. The peptide in which pyroglutamate at position 1 was replaced gave a truncated inositol phosphate response whereas all other peptides produced full responses with varying sensitivities. The sensitivity of response to the analogue in which threonine at position 6 was replaced was considerably higher than that of the native hormone. None of the inactive or partially active peptides appeared to block the action of adipokinetic hormone-1 or -2. All peptides that were active in the inositol phosphate assay also stimulated the accumulation of cyclic AMP. Some similarities were found in the relative activities of the peptides in the two assay systems.