Effect of amino acids on isolated colonic smooth muscle from the rabbit

The purpose of these studies was to evaluate the direct effect of amino acids on rabbit colonic smooth muscle. Isometric tension was measured in circular smooth muscle from the distal colon after the administration of 19 individual L-amino acids. L-Alanine, L-cysteine, L-serine and L-methionine stimulated a dose-dependent increase in isometric tension. The lowest concentration which increased tension of the tissue for each of these amino acids was between 1 X 10(-4) to 5 X 10(-4) M. At a concentration of 10(-3) M, each of these four amino acids stimulated smooth muscle to 40 to 60% of the maximum response to bethanechol (2050 +/- 105 mN/m2). The 15 other amino acids tested had less effect on the colonic smooth muscle. The smooth muscle response to the D-amino acids, D-alanine, D-cysteine or D-serine, was shifted 10-fold to the right. Neural blockade by tetrodotoxin, the alpha adrenergic receptor antagonist, phentolamine, or the alpha-2 antagonist, yohimbine, increased smooth muscle tension, but did not inhibit L-amino acid stimulation of the tissue. Atropine, naloxone or prazosin (alpha-1 adrenergic antagonist) had no effect on amino acid stimulation of the muscle. These data suggest that L-amino acids, alanine, serine, cysteine and methionine stimulate contraction of colonic circular smooth muscle, this response is stereospecific and amino acids appear to stimulate the smooth muscle directly and not through an effect on the myenteric neurons.