Abstract
1. The localization, tissue concentrations, and effects of pituitary adenylate cyclase activating peptide (PACAP) 27 and 38 were investigated in cat and human lower oesophageal sphincter (LOS), and compared with those of vasoactive intestinal peptide (VIP) and helospectin. 2. PACAP-immunoreactive nerve structures were found in the cat and human LOS, with an abundance in the circular smooth muscle layer. PACAP 27-immunoreactivity was often co-localized with VIP-immunoreactivity. 3. In cat tissue, PACAP (PACAP 27 plus PACAP 38) concentrations were 50 fold lower than VIP concentrations; in human tissue they were 10 fold lower. 4. PACAP 27, PACAP 38, helospectin I, and VIP induced concentration-dependent relaxations in circular smooth muscle preparations from cat and human LOS. The order of potency was: VIP > helospectin I > or = PACAP 27 > PACAP 38. NG-nitro-L-arginine, scopolamine, or apamin, did not influence the relaxant effects of PACAP 27 or VIP. 5. In cat preparations, both cyclic AMP and cyclic GMP levels were increased after exposure to PACAP 27 and helospectin I, whereas exposure to VIP was followed by an increase in cyclic AMP levels only. In human preparations, there was an increase in cyclic AMP levels without any change in cyclic GMP levels. 6. These results suggest that in the cat and human LOS, PACAP 27 and VIP can occur within the same nerve structures. PACAP 27 has a potent relaxant action, but its functional importance has to be established.
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Selected References
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- Absood A., Ekblad E., Ekelund M., Håkanson R., Sundler F. Helospectin-like peptides in the gastrointestinal tract: immunocytochemical localization and immunochemical characterization. Neuroscience. 1992;46(2):431–438. doi: 10.1016/0306-4522(92)90063-8. [DOI] [PubMed] [Google Scholar]
- Aggestrup S., Uddman R., Jensen S. L., Håkanson R., Sundler F., Schaffalitzky de Muckadell O., Emson P. Regulatory peptides in lower esophageal sphincter of pig and man. Dig Dis Sci. 1986 Dec;31(12):1370–1375. doi: 10.1007/BF01299816. [DOI] [PubMed] [Google Scholar]
- Alumets J., Schaffalitzky de Muckadell O., Fahrenkrug J., Sundler F., Håkanson R., Uddman R. A rich VIP nerve supply is characteristic of sphincters. Nature. 1979 Jul 12;280(5718):155–156. doi: 10.1038/280155a0. [DOI] [PubMed] [Google Scholar]
- Arimura A. Pituitary adenylate cyclase activating polypeptide (PACAP): discovery and current status of research. Regul Pept. 1992 Feb 18;37(3):287–303. [PubMed] [Google Scholar]
- Biancani P., Walsh J. H., Behar J. Vasoactive intestinal polypeptide. A neurotransmitter for lower esophageal sphincter relaxation. J Clin Invest. 1984 Apr;73(4):963–967. doi: 10.1172/JCI111320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Christophe J. Type I receptors for PACAP (a neuropeptide even more important than VIP?). Biochim Biophys Acta. 1993 Oct 29;1154(2):183–199. doi: 10.1016/0304-4157(93)90011-c. [DOI] [PubMed] [Google Scholar]
- De Man J. G., Pelckmans P. A., Boeckxstaens G. E., Bult H., Oosterbosch L., Herman A. G., Van Maercke Y. M. The role of nitric oxide in inhibitory non-adrenergic non-cholinergic neurotransmission in the canine lower oesophageal sphincter. Br J Pharmacol. 1991 May;103(1):1092–1096. doi: 10.1111/j.1476-5381.1991.tb12305.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Desai H., Uddman R., Malina J., Sundler F. Helospectin-like immunoreactivity in the esophagus. Regul Pept. 1992 Aug 13;40(3):363–371. doi: 10.1016/0167-0115(92)90523-w. [DOI] [PubMed] [Google Scholar]
- Fahrenkrug J., Schaffalitzky de Muckadell O. B. Distribution of vasoactive intestinal polypeptide (VIP) in the porcine central nervous system. J Neurochem. 1978 Dec;31(6):1445–1451. doi: 10.1111/j.1471-4159.1978.tb06571.x. [DOI] [PubMed] [Google Scholar]
- Fahrenkrug J., Schaffalitzky de Muckadell O. V. Radioimmunoassay of vasoactive intestinal polypeptide (VIP) in plasma. J Lab Clin Med. 1977 Jun;89(6):1379–1388. [PubMed] [Google Scholar]
- Goyal R. K., Rattan S., Said S. I. VIP as a possible neurotransmitter of non-cholinergic non-adrenergic inhibitory neurones. Nature. 1980 Nov 27;288(5789):378–380. doi: 10.1038/288378a0. [DOI] [PubMed] [Google Scholar]
- Hannibal J., Mikkelsen J. D., Clausen H., Holst J. J., Wulff B. S., Fahrenkrug J. Gene expression of pituitary adenylate cyclase activating polypeptide (PACAP) in the rat hypothalamus. Regul Pept. 1995 Jan 26;55(2):133–148. doi: 10.1016/0167-0115(94)00099-j. [DOI] [PubMed] [Google Scholar]
- Ishihara T., Shigemoto R., Mori K., Takahashi K., Nagata S. Functional expression and tissue distribution of a novel receptor for vasoactive intestinal polypeptide. Neuron. 1992 Apr;8(4):811–819. doi: 10.1016/0896-6273(92)90101-i. [DOI] [PubMed] [Google Scholar]
- Jin J. G., Katsoulis S., Schmidt W. E., Grider J. R. Inhibitory transmission in tenia coli mediated by distinct vasoactive intestinal peptide and apamin-sensitive pituitary adenylate cyclase activating peptide receptors. J Pharmacol Exp Ther. 1994 Aug;270(2):433–439. [PubMed] [Google Scholar]
- Johnson G. D., Nogueira Araujo G. M. A simple method of reducing the fading of immunofluorescence during microscopy. J Immunol Methods. 1981;43(3):349–350. doi: 10.1016/0022-1759(81)90183-6. [DOI] [PubMed] [Google Scholar]
- Katsoulis S., Clemens A., Schwörer H., Creutzfeldt W., Schmidt W. E. PACAP is a stimulator of neurogenic contraction in guinea pig ileum. Am J Physiol. 1993 Aug;265(2 Pt 1):G295–G302. doi: 10.1152/ajpgi.1993.265.2.G295. [DOI] [PubMed] [Google Scholar]
- Keef K. D., Shuttleworth C. W., Xue C., Bayguinov O., Publicover N. G., Sanders K. M. Relationship between nitric oxide and vasoactive intestinal polypeptide in enteric inhibitory neurotransmission. Neuropharmacology. 1994 Nov;33(11):1303–1314. doi: 10.1016/0028-3908(94)90030-2. [DOI] [PubMed] [Google Scholar]
- McConalogue K., Furness J. B., Vremec M. A., Holst J. J., Tornøe K., Marley P. D. Histochemical, pharmacological, biochemical and chromatographic evidence that pituitary adenylyl cyclase activating peptide is involved in inhibitory neurotransmission in the taenia of the guinea-pig caecum. J Auton Nerv Syst. 1995 Jan 3;50(3):311–322. doi: 10.1016/0165-1838(94)00102-p. [DOI] [PubMed] [Google Scholar]
- McGregor G. P., Bishop A. E., Blank M. A., Christofides N. D., Yiangou Y., Polak J. M., Bloom S. R. Comparative distribution of vasoactive intestinal polypeptide (VIP), substance P and PHI in the enteric sphincters of the cat. Experientia. 1984 May 15;40(5):469–471. doi: 10.1007/BF01952390. [DOI] [PubMed] [Google Scholar]
- Miyata A., Arimura A., Dahl R. R., Minamino N., Uehara A., Jiang L., Culler M. D., Coy D. H. Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun. 1989 Oct 16;164(1):567–574. doi: 10.1016/0006-291x(89)91757-9. [DOI] [PubMed] [Google Scholar]
- Miyata A., Jiang L., Dahl R. D., Kitada C., Kubo K., Fujino M., Minamino N., Arimura A. Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38). Biochem Biophys Res Commun. 1990 Jul 31;170(2):643–648. doi: 10.1016/0006-291x(90)92140-u. [DOI] [PubMed] [Google Scholar]
- Moller K., Zhang Y. Z., Håkanson R., Luts A., Sjölund B., Uddman R., Sundler F. Pituitary adenylate cyclase activating peptide is a sensory neuropeptide: immunocytochemical and immunochemical evidence. Neuroscience. 1993 Dec;57(3):725–732. doi: 10.1016/0306-4522(93)90018-b. [DOI] [PubMed] [Google Scholar]
- Mungan Z., Arimura A., Ertan A., Rossowski W. J., Coy D. H. Pituitary adenylate cyclase-activating polypeptide relaxes rat gastrointestinal smooth muscle. Scand J Gastroenterol. 1992 May;27(5):375–380. doi: 10.3109/00365529209000091. [DOI] [PubMed] [Google Scholar]
- Murthy K. S., Makhlouf G. M. Vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide-dependent activation of membrane-bound NO synthase in smooth muscle mediated by pertussis toxin-sensitive Gi1-2. J Biol Chem. 1994 Jun 10;269(23):15977–15980. [PubMed] [Google Scholar]
- Ny L., Alm P., Ekström P., Hannibal J., Larsson B., Andersson K. E. Nitric oxide synthase-containing, peptide-containing, and acetylcholinesterase-positive nerves in the cat lower oesophagus. Histochem J. 1994 Sep;26(9):721–733. doi: 10.1007/BF00158204. [DOI] [PubMed] [Google Scholar]
- Ny L., Alm P., Larsson B., Ekström P., Andersson K. E. Nitric oxide pathway in cat esophagus: localization of nitric oxide synthase and functional effects. Am J Physiol. 1995 Jan;268(1 Pt 1):G59–G70. doi: 10.1152/ajpgi.1995.268.1.G59. [DOI] [PubMed] [Google Scholar]
- Parker D. S., Raufman J. P., O'Donohue T. L., Bledsoe M., Yoshida H., Pisano J. J. Amino acid sequences of helospectins, new members of the glucagon superfamily, found in Gila monster venom. J Biol Chem. 1984 Oct 10;259(19):11751–11755. [PubMed] [Google Scholar]
- Schwörer H., Katsoulis S., Creutzfeldt W., Schmidt W. E. Pituitary adenylate cyclase activating peptide, a novel VIP-like gut-brain peptide, relaxes the guinea-pig taenia caeci via apamin-sensitive potassium channels. Naunyn Schmiedebergs Arch Pharmacol. 1992 Nov;346(5):511–514. doi: 10.1007/BF00169005. [DOI] [PubMed] [Google Scholar]
- Sundler F., Ekblad E., Absood A., Håkanson R., Köves K., Arimura A. Pituitary adenylate cyclase activating peptide: a novel vasoactive intestinal peptide-like neuropeptide in the gut. Neuroscience. 1992;46(2):439–454. doi: 10.1016/0306-4522(92)90064-9. [DOI] [PubMed] [Google Scholar]
- Szewczak S. M., Behar J., Billett G., Hillemeier C., Rhim B. Y., Biancani P. VIP-induced alterations in cAMP and inositol phosphates in the lower esophageal sphincter. Am J Physiol. 1990 Aug;259(2 Pt 1):G239–G244. doi: 10.1152/ajpgi.1990.259.2.G239. [DOI] [PubMed] [Google Scholar]
- Torphy T. J., Fine C. F., Burman M., Barnette M. S., Ormsbee H. S., 3rd Lower esophageal sphincter relaxation is associated with increased cyclic nucleotide content. Am J Physiol. 1986 Dec;251(6 Pt 1):G786–G793. doi: 10.1152/ajpgi.1986.251.6.G786. [DOI] [PubMed] [Google Scholar]
- Tøttrup A., Forman A., Uldbjerg N., Funch-Jensen P., Andersson K. E. Mechanical properties of isolated human esophageal smooth muscle. Am J Physiol. 1990 Mar;258(3 Pt 1):G338–G343. doi: 10.1152/ajpgi.1990.258.3.G338. [DOI] [PubMed] [Google Scholar]
- Tøttrup A., Ny L., Alm P., Larsson B., Forman A., Andersson K. E. The role of the L-arginine/nitric oxide pathway for relaxation of the human lower oesophageal sphincter. Acta Physiol Scand. 1993 Dec;149(4):451–459. doi: 10.1111/j.1748-1716.1993.tb09642.x. [DOI] [PubMed] [Google Scholar]
- Tøttrup A., Svane D., Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol. 1991 Mar;260(3 Pt 1):G385–G389. doi: 10.1152/ajpgi.1991.260.3.G385. [DOI] [PubMed] [Google Scholar]
- Uddman R., Luts A., Absood A., Arimura A., Ekelund M., Desai H., Håkanson R., Hambreaus G., Sundler F. PACAP, a VIP-like peptide, in neurons of the esophagus. Regul Pept. 1991 Nov 26;36(3):415–422. doi: 10.1016/0167-0115(91)90074-q. [DOI] [PubMed] [Google Scholar]
- Wessendorf M. W., Elde R. P. Characterization of an immunofluorescence technique for the demonstration of coexisting neurotransmitters within nerve fibers and terminals. J Histochem Cytochem. 1985 Oct;33(10):984–994. doi: 10.1177/33.10.2413102. [DOI] [PubMed] [Google Scholar]