THE CALCITONIN-GENE-RELATED PEPTIDE ACTIVATES BOTH CAMP AND NO PATHWAYS TO INDUCE RELAXATION OF CIRCULAR SMOOTH-MUSCLE CELLS OF GUINEA-PIG ILEUM

The direct effects and the intracellular pathways of rCGRP were invest igated on smooth muscle cells (SMC) isolated by enzymatic digestion fr om the circular and longitudinal layers of guinea-pig ileum. In circul ar SMC, rCGRP inhibited CCK8-induced contraction in a concentration-de pendent manner (Cmax = 100 mu M and EC50 = 0.7 +/- 0.4 nM). Preincubat ion of SMC with 1 mu M Rp-cAMPs, a cAMP antagonist, abolished the rela xing effect of rCGRP; moreover, preincubation of SMC with 100 mu M L-N AME, an inhibitor of NOS, inhibited the relaxing effect of rCGRP. hCGR P(8-37), a selective antagonist of rCGRP receptors, inhibited the rCGR P-induced relaxation in a concentration dependent manner whereas the v asoactive intestinal polypeptide (VIP) antagonist had no significant e ffect. In longitudinal SMC, rCGRP-induced relaxation was abolished by Rp-cAMPs, whereas L-NAME had no effect. In conclusion, rCGRP triggers different intracellular pathways to induce relaxation of circular or l ongitudinal intestinal SMC; cAMP is involved in cells from both layers while nitric oxide (NO) is involved only in relaxation of circular SM C. (C) 1997 Elsevier Science Inc.