Chemical and Biological Properties of Porcine Secretin and Secretin Analogues Modified in Positions 3 and 4

In vivo effects of five secretin analogs on fluid and potassium secretion from the rat pancreas

“…2 and 3). The substitution of aspartic acid residue in position 3 by the more hydrophobic glutamic acid provoked already a definite décline in biological activity, in line with similar data on fluid sécrétion from the dog pancréas (13). The neutralization of the acidic function of aspartic acid into asparagine markedly reduced the potency, as was already shown to be the case on fluid sécrétion from the isolated perfused cat pancréas, when aspartic acid is replaced by glutamine (the amino acid residue présent in the 3 position of the parent peptide glucagon) (14).…”

“…2 and 3) but the time-study of their effects did not suggest any increase in the résistance of such peptides to in vivo dégradation (data not shown). The présent data on the rat pancréas were at variance with in vivo data on dog showing that [Ala^jsecretin and [D-Ala^]secretin exhibit, respectively, 2 and 8 % only of secretin activity (13) and with in vitro data on guinea pig acinar cells (16) showing that [Ala^, Tyr10]secretin is 10-fold less potent than [Tyr10]secretin.…”

Specificity of receptors to vasoactive intestinal peptide in guinea pig brain

“…[Ala^]secretin and its stereoisomer [D-Ala^]secretin were inactive although an alanine residue is présent in the 4 position of the VIP molécule. Similarly, Konig et al (6) reported that [Ala4]secretin and [D-Ala4]secretin were only 2 % and 8 % as active, respectively, as secretin on dog pancréas. On rat pancréas, [ Al a4] secret in and [D-Ala^]secretin are 20-fold less potent than secretin on adenylate cyclase activation but equipotent to secretin for inhibiting 125i-viP binding (9).…”

“…The substitution of the aspartic acid residue in position 3 of secretin by glutamic acid or asparagine made thèse two peptides unable to occupy VIP_c receptors in guinea pig brain membranes even when offered at a high 4.10" M concentration. The same peptides exert a markedly reduced activity on pancreatic function (6) and pancreatic adenylate cyclase (9) when compared to secretin.…”

“…secretin and the C-terminal secretin fragment(7-27) were prepared as previously described (6,7). Natural porcine glucagon was provided by Novo Industri (Etablissements Couvreur, Brussels, Belgium).…”