STRUCTURE-FUNCTION STUDIES ON HYPERTREHALOSEMIC AND ADIPOKINETIC HORMONES - ACTIVITY OF NATURALLY-OCCURRING ANALOGS AND SOME N-TERMINAL AND C-TERMINAL MODIFIED ANALOGS

Abstract The relative potencies, with respect to mobilization of lipids in Locusta migratoria L. and in Schistocerca gregaria Forsk. and of carbohydrates in Periplaneta americana L., of eleven naturally‐occurring members of the AKH/RPCH‐family of peptides and of some analogues that lacked the N‐terminal pyroglutamate residue or had a free threonine acid at the C‐terminus instead of an amide are assessed. The time courses for carbohydrate and lipid release shown for the peptides suggest that their transport and degradation rates are similar. Therefore, their relative activities reflect most probably the different abilities to bind to the receptors on the fat body cells of the cockroaches and locusts tested. The results show clearly that the N‐ and C‐terminally modified analogues give poor or almost no responses regardless of the bioassay employed. Compared with the structural requirements of the cockroach receptor(s), the receptor(s) of the locusts appear more specific. In the cockroach bioassay, only the two octapeptides Lom‐AKH‐II and Grb‐AKH, both lacking a proline residue at position 6, have high ED50 values, whereas the ED50 values of all other peptides are between 0.4 and 2.7 pmol. The exception is the nonapeptide Mas‐AKH, lacking proline and having a serine residue at position 7 (a unique feature compared with the other peptides): no activity is exerted below 100 pmol and only a poor response is elicited with higher dosages. The L. migratoria receptor(s) bind the decapeptides best (exception: Bld‐HrTH). Octapeptides, even Scg‐AKH‐II and Grb‐AKH which lack a proline residue, elicit a maximum response, but ED50 values are 7–15‐fold higher than with Lom‐AKH‐I. Lom‐AKH‐II, however, gives only a truncated response. The nonapeptide Mas‐AKH is able to elicit a maximum response, but 50 pmol are needed instead of 2 pmol (Lom‐AKH‐I). In 5.gregaria a maximum response is achieved with Lom‐AKH‐I and Grb‐AKH, but injections of Scg‐AKH‐II, Lom‐AKH‐II and Rom‐CC‐I result in only truncated responses. The importance of a β‐turn in the molecules and the presence of proline is discussed. No evidence is found for an antagonistic effect on binding of those peptides that fail to achieve maximum responses. Copyright © 1990, Wiley Blackwell. All rights reserved