Martin Bickel

Motilin and a synthetic enkephalin induce colonic motor complexes (CMC) in the conscious dog

In the conscious dog migrating and nonmigrating colonic motor complexes (CMC) were recorded by means of chronically implanted strain gauge force transducers. Intravenous injection of a synthetic enkephalin analogue immediately induced a premature CMC at all three recording sites of the colon. Naloxone inhibited the enkephalin- but not motilin-induced CMC. We therefore exclude that motilin acts by release of endogenous enkephalins. The two peptides stimulate CMC in the canine colon by different pathways. Naloxone alone had no effect on normal colonic motility, suggesting strongly that endogenous enkephalins do not modulate regular CMC in the dog.

Analogues and fragments of secretin

Abstract For the purpose of analytical investigation and structure/activity relationships, some secretin analogues and secretin fragments have been synthesized. HPLC comparison of the synthesized products with our synthetic secretin revealed about 2% [D-Ala 17 ]secretin, 1% [D-Leu 13 ]secretin and less than 1% aminoterminal degradation products. The D-Ala 17 content can be eliminated if the starting material used for segment coupling (Z-Arg(Z 2 )-Asp(OBu 1 )- Ala -OH) has no D-Ala-contamination. In addition, traces of the rearrangement products [3-aspartoyl]-secretin and [β-Asp 3 ]secretin are suspected. Secretin can be degraded to several compounds by chromatography on a strong basic ion exchanger in 1% acetic acid. These products are more polar than secretin and have no biological activity. The secretin content measured by HPLC correlated well with the biological data, since the degradation products and other byproducts separated by HPLC have only a negligible influence on the pancreatic flow.

New analogues of secretin.

For the evaluation of structure/activity relationships, some porcine secretin analogues, modified in the N-terminus, have been synthesized by segment condensation in solution. The secretin activity of the analogues was defined as the volume of pancreatic juice secreted in rats and dogs. The exchange of the N-terminal pentapeptide for the N-terminal pentapeptide of human somatotropin releasing factor (h-SRF) resulted in a peptide ([1-Tyr,2,4-Di-Ala,5-Ile]secretin) with practically no SRF-activity (less than 1% SRF-activity up to 100 micrograms/kg in the rat), but surprisingly high secretin activity (almost 100% in the rat, but only 1150 CU/mg (27%) in the dog). [3-L-Cysteic acid]secretin showed 1750 CU/mg (39%) in the dog, but a less activity (23%) in the rat. [6-D-Phe]secretin and [5-D-allo-Thr]secretin are again strongly species specific. They exhibited an activity of less than 1% in the dog, but about 10-15% in the rat. The smallest secretin activity was observed with [1-Cys,6-Cys]secretin in the oxidized form. The activity in the rat with this analogue was only about 0.2%.