Lysine ¹⁴Galanin(1–15)-IMH₂: A Partial Agonist at Galanin Receptors in Rat Isolated Gastric Fundus

Abstract

The study was undertaken to characterize the effects of the porcine galanin [pGal(1–29)-NH2] analogue [Lys¹⁴]pGal(1–15)-NH₂ on rat gastric fundus. [Lys¹⁴]pGal(1–15)-NH₂ is a less potent contractile agent than pGal(1–29)-NH₂ (EC₅₀ 74.1 vs. 43.7 nmol/l, respectively) and shows a significantly lower maximal response than pGal(1–29)-NH2. Concentration-contraction curves were constructed for pGal(1–29)-NH₂ alone (control) and pGal(1–29)-NH₂ in the presence of 10, 100, and 1,000 nmol/l of [Lys¹⁴]pGal(1–15)-NH₂. [Lys¹⁴]pGal(1–15)-NH₂ shifted the concentration-contraction curves of pGal(1–29)-NH₂ significantly to the right, whereas their linear portions remained parallel to that for the pGal(1–29)-NH₂ control. [Lys¹⁴]pGal(1–15)-NH₂ markedly increased the EC₅₀ of the respective pGal(1–29)-NH₂ concentration-contraction curves. It did not substantially change the maximal response of the muscles to pGal(1–29)-NH₂ and the form of the respective concentration-contraction curves. Schild’s plot gave a straight line with a slope of 0.84. The pA₂ value for [Lys¹⁴]pGal(1–15)-NH₂ was 8.23. [Lys¹⁴]pGal(1–15)-NH₂seems to be a partial Gal receptor agonist. Since the lack of specific Gal receptor antagonists in the gastrointestinal tract makes a precise characterization of its role as a motility modulator difficult, the position 14 in the pGal(1–29)-NH₂ molecule looks as an attractive target in the search of a pure Gal receptor antagonist in the smooth muscles of the gut.