Functional CCK-A and Y2 receptors in guinea pig esophagus.
Effects of cholecystokinin octapeptide (CCK-8), peptide YY (PPY), neuropeptide Y (NPY) and their analogs on muscle contractions of esophageal strips were investigated. CCK-8 induced a tetrodotoxin and atropine-sensitive contraction. The relative potencies for CCK related peptides to induce contractions were CCK-8 > desulfated CCK-8 > gastrin-17-I. The CCK-A receptor antagonist L-364,718 was 300-fold more potent than the CCK-B receptor antagonist L-365,260 at inhibiting CCK-8-induced contraction. These indicate that neural CCK-A receptors mediate this contraction. PYY or NPY did not cause muscle contraction or inhibit muscle contraction induced by carbachol, endothelin-1 or KCl. However, both PYY and NPY concentration-dependently inhibited contraction induced by CCK-8. This inhibition was not affected by nitric oxide (NO) synthase inhibitors L-NMMA or L-NAME. The relative potencies of PYY related peptides to inhibit CCK-8 induced contraction were PYY > NPY > NPY13-36 > [Leu(31), Pro(34)]NPY > pancreatic polypeptide (PP). We conclude that CCK interacts with neural CCK-A receptors to cause esophageal muscle contraction. PYY and NPY interact with Y2 receptors to inhibit this CCK-induced muscle contraction by an effect not related to NO.
Huang
S C
SC
Department of Internal Medicine, Tzu Chi General Hospital and Tzu Chi College of Medicine and Humanities, 707, Section 3, Chung-Yang Road, Hualien, Taiwan, ROC. shihche@mail.tcu.edu.tw
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000031:analogs & derivatives; D020109:Devazepide / Q000494:pharmacology; D004594:Electrophysiology; D004947:Esophagus / Q000187:drug effects / Q000502:physiology*; D006168:Guinea Pigs; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000494:pharmacology; D019894:Peptide YY / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*; D017476:Receptors, Neuropeptide Y / Q000502:physiology*
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D009478:Neuropeptide Y; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D019894:Peptide YY; C058121:L 365260; D002766:Cholecystokinin; D020109:Devazepide