Actions of several substituted short analogues of porcine galanin on isolated rat fundus strips: A structure-activity relationship

The activity of porcine galanin (Gal) fragments and analogues were tested i n vitro using rat gastric fundus strips. The peptides contracted longitudin al smooth muscle in a concentration-dependent manner with the following ord er of potency: [Nle(4)]Gal(1-15), Gal(1-15), [Cle(4)]Gal(1-15), [Hse(6)]Gal (1-15), [Val(4)]Gal(1-15), [Ile(4)]Gal(1-15), [endoTrip(2a), Cle(4)]Gal(1-1 5), [desThr(3), Cle(4)]Gal (1-15), [D-Leu(4)] Gal(1-15), [desLeu(4)]Gal(1-1 5). On the contrary [desTrp(2),Val(4)]Gal (1-15) remained inactive up to 10 muM. The values of Hill's coefficients estimated from the appropriate conc entration-contraction curves for all analogues except for [Val(4)]Gal (1-15 ), [Hse(6)]Gal (1-15), [endoTrp(2a), Cle(4)]Gal (1-15), [desLeu(4)]Gal (1-1 5) and [D-Leu(4)] Gal (1-15) did not significantly differ from unity. Our r esults indicate that the integrity of the first four N-terminal amino acids of Gal molecule is essential for the full excitatory myogenic action of th e peptide in rat gastric fundus. Similarly, substitution, addition or delet ion of amino acid residues in positions two, three, four and six can consid erably influence the ability of Gal analogues to interact with Gal receptor s. The data acquired in the course of our structure-activity study suggest that both N- and C-terminals of Gal molecule contribute towards the affinit y and activity of Gal in rat gastric smooth muscle cell receptors.