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 investigated on smooth muscle cells (SMC) isolated by enzymatic digestion from the circular and longitudinal layers of guinea-pig ileum. In circular SMC, rCGRP inhibited CCK8-induced contraction in a concentration-dependent manner (Cmax = 100 microM and EC50 = 0.7 +/- 0.4 nM). Preincubation of SMC with 1 microM Rp-cAMPs, a cAMP antagonist, abolished the relaxing effect of rCGRP; moreover, preincubation of SMC with 100 microM L-NAME, an inhibitor of NOS, inhibited the relaxing effect of rCGRP, hCGRP(8-37), a selective antagonist of rCGRP receptors, inhibited the rCGRP-induced relaxation in a concentration dependent manner whereas the vasoactive intestinal polypeptide (VIP) antagonist had no significant effect. 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 longitudinal intestinal SMC; cAMP is involved in cells from both layers while nitric oxide (NO) is involved only in relaxation of circular SMC.
Rekik
M
M
Department of Pharmacology, INRA, Toulouse, France.
Delvaux
M
M
Frexinos
J
J
Bueno
L
L
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D011994:Recombinant Proteins; D013873:Thionucleotides; C058636:calcitonin gene-related peptide (8-37); C016957:adenosine-3',5'-cyclic phosphorothioate; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001120:Arginine; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D012844:Sincalide; D019331:NG-Nitroarginine Methyl Ester