Skip to main content
SpringerLink
Log in

Investigation of Endogenous of Guinea Pig Gallbladder Using Nicotinic Agonist Stimulation

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Gallbladder motility is modulated by intrinsicnerves, the identities of which are not wellestablished. The aim of this study was to determine theeffect of nicotinic receptor stimulation of intrinsic nerves on gallbladder muscle contractility.Guinea pig gallbladder muscle strips were studied invitro . Histamine 1 μM was used to increase baselinetone. The nicotinic receptor agonist,1,1-dimethyl-4-phenylpiperazinium (DMPP), produced a biphasic responsecharacterized by an initial transient contractionfollowed by a sustained relaxation. The initialcontraction was inhibited by the neural blockertetrodotoxin, the nicotinic antagonist hexamethonium, and the muscarinicantagonist atropine, but not by a substance P receptorantagonist or a bombesin receptor antagonist. Therelaxation response to DMPP was not affected bytetrodotoxin, but was reduced by hexamethonium andomega-conotoxin GVIA, an inhibitor of neurotransmitterrelease. The relaxation response was reduced by thenitric oxide synthase inhibitor L-NAME, but not by avasoactive intestinal peptide antagonist or propranolol.DMPP produces a biphasic response in the guinea piggallbladder. The initial contractile response ismediated by nicotinic receptors on the cell body or axon of cholinergic nerves. The relaxation responseappears to result, in part, from activation of nicotinicreceptors on nerve terminals of nitric oxide-releasingnerves. These results suggest nicotinic receptors have heterogeneity in location depending onexcitatory or inhibitory neuronal function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Yau WM, Youther ML: Modulation of gallbladder motility by intrinsic cholinergic neurons. Am J Physiol 247:G662-G666, 1984

    PubMed  Google Scholar 

  2. Brotschi EZ, Pattavino J, Williams LF: Intrinsic nerves affect gallbladder contraction in the guinea pig. Gastroenterology 99:826-830, 1990

    PubMed  Google Scholar 

  3. Fisher RS, Rock E, Malmud LS: Cholinergic effects on gallbladder emptying in humans. Gastroenterology 89:716-722, 1985

    PubMed  Google Scholar 

  4. Hanyu N, Dodds WJ, Layman RD, Hogan WJ, Chey WJ, Takahashi I: Mechanism of cholecystokinin-induced contraction of the opossum gallbladder. Gastroenterology 98:1299- 1306, 1990

    PubMed  Google Scholar 

  5. Takahashi T, May D, Owyang C: Cholinergic dependence of gallbladder response to cholecystokinin in the guinea pig in vivo. Am J Physiol 261:G565-G569, 1991

    PubMed  Google Scholar 

  6. Mawe GM: Tachykinins as mediators of slow EPSPs in guineapig gall-bladder ganglia: Involvement of neurokinin-3 receptors. J Physiol 485:513-524, 1995

    PubMed  Google Scholar 

  7. Schjoldager B, Poulsen SS, Schmidt P, Coy DH, Holst JJ: Gastrin-releasing peptide is a transmitter mediating porcine gallbladder contraction: Am J Physiol 260:G577-G585, 1991

    PubMed  Google Scholar 

  8. Mourelle M, Guarner F, Moncada S, Malagelada J-R: The L-arginine:nitric oxide pathway regulates gallbladder motility in the guinea pig. Gut 34:911-915, 1993

    PubMed  Google Scholar 

  9. Sundler F, Alumets J, Hakanson R, Ingemansson S, Fahrenkrug J, de Muckadell OS: VIP innervation of the gallbladder. Gastroenterology 72:1375-1377, 1977

    PubMed  Google Scholar 

  10. Chen O, Lee KY, Biancani P, Behar J: Mechanisms of gallbladder relaxation in the cat. Dig Dis Sci 41:1882, 1996 (abstract)

    Google Scholar 

  11. Davison JS, Al-Hassani M, Crowe R, Burnstock G: The nonadrenergic, inhibitory innervation of the guinea-pig gallbladder. Pfluegers Arch 377:43-49, 1978

    Google Scholar 

  12. Parkman HP, Pagano AP, Martin JS, Ryan JP: Electric field stimulation (EFS) induced guinea pig gallbladder contractions: Role of calcium channels in acetylcholine release. Dig Dis Sci 41:1881, 1996 (abstract)

    Google Scholar 

  13. Mourelle M, Guarner F, Moncada S, Malagelada J-R: The arginine/nitric oxide pathway modulates sphincter of Oddi motor activity in guinea pigs and rabbits. Gastroenterology 105:1299-1305, 1993

    PubMed  Google Scholar 

  14. Takahashi T, Tsunoda Y, Lu Y, Wiley J, Owyang C: Nicotinic receptor-evoked re lease of acetylcholine and somatostatin in the mye nteric plexus is coupled to calcium influx via N-type calcium channels. J Pharm Exp Ther 263:1-5, 1992

    Google Scholar 

  15. Chakder S, Rattan S: Release of nitric oxide by activation of nonadrenergic noncholinergic neurons of internal anal sphincter. Am J Physiol 264:G7-G12, 1993

    PubMed  Google Scholar 

  16. Parkman HP, Pagano AP, Ryan JP: Dual effects of PACAP on guinea pig gallbladder muscle via PACAP-preferring and VIP/ PACAP-preferring receptors. Am J Physiol 272:G1433-G1438, 1997

    PubMed  Google Scholar 

  17. Cai W-Q, Gabella G: Innervation of the gallbladder and biliary pathways in the guinea pig. J Anat 136:97-109, 1983

    PubMed  Google Scholar 

  18. Talmage EK, Pouliot WA, Schemann M, Mawe GM: Structure and chemical coding of human, canine and opossum gallbladder ganglia. Cell Tissue Res 284:289-302, 1996

    PubMed  Google Scholar 

  19. Talmage EK, Mawe GM: NADPH-diaphorase and VIP are co-localized in neurons of gallbladder ganglia. J Auton Nerv Sys 43:83-90, 1993

    Google Scholar 

  20. Murthy KS, Zhang KM, Jin JG, Grider JR, Makhlouf GM: VIP-mediated G protein-coupled Ca21 influx activates a constitive NOS in dispersed gastric muscle cells. Am J Physiol 265:G660-G671, 1993

    PubMed  Google Scholar 

  21. Salomons H, Keaveny AP, Henihan R, Offner G, Sengupta A, LaMorte WW, Afdhal NH: Nitric oxide and gallbladder motility in prairie dogs. Am J Physiol 272:G770-G778, 1997

    PubMed  Google Scholar 

  22. Grider JR, Jin J-G: Vasoactive intestinal peptide release and l-citrulline production from isolated ganglia of the myenteric plexus: Evidence for regulation of vasoactive intestinal peptide release by nitric oxide. Neuroscience 54:521-526, 1993

    PubMed  Google Scholar 

  23. Shuttleworth CWR, Weinert JS, Sanders KM, Buxton ILO: Detection of nitric oxide from canine enteric neurons. J Autonom Nerv Syst 56:61-68, 1995

    Google Scholar 

  24. Dolezal V, Schobert A, Hertting G: Presynaptic nicotinic receptors stimulate increases in intraterminal calcium of chick sympathetic neurons in culture. J Neurochem 65:1874-1879, 1995

    PubMed  Google Scholar 

  25. McCleskey EW, Fox AP, Feldman DH, Cruz LJ, Olivera BM, Tsien RW, Yoshikami D: Omega-conotoxin: Direct and persistent blockade of specific type s of calcium channels in neurons but not muscle. Proc Natl Acad Sci USA 84:4327-4331, 1987

    PubMed  Google Scholar 

  26. Lukas RJ: Nicotinic ace tylcholine receptor diversity: Agonist binding and functional potency. Prog Brain Res 79:117-127, 1989

    PubMed  Google Scholar 

  27. Sargent PB: The diversity of neuronal nicotinic ace tylcholine receptors. Annu Rev Neurosci 16:403-443, 1993

    PubMed  Google Scholar 

  28. Varanda WA, Aracava Y, Sherry SM, VanMeter WG, Eldefrawi ME, Albuquerque EX: The ace tylcholine receptor of the neuromuscular junction recognize s mecamylamine as a noncompetitive antagonist. Mol Pharmacol 28:128-137, 1985

    PubMed  Google Scholar 

  29. Lukas RJ, Bencherif M: Heterogeneity and regulation of nicotinic acetylcholine receptors. Int Rev Neurobiol 34:25-115, 1992

    PubMed  Google Scholar 

  30. Talmage EK, Pouliot WA, Cornbrooks EB, Mawe GM: Transmitter diversity in ganglion cells of the guinea pig gallbladder: An immunohistochemistry study. J Comp Neurol 317:45-56, 1992

    PubMed  Google Scholar 

Download references

Authors
  1. Henry P. Parkman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony P. Pagano
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James P. Ryan
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Parkman, H.P., Pagano, A.P. & Ryan, J.P. Investigation of Endogenous of Guinea Pig Gallbladder Using Nicotinic Agonist Stimulation. Dig Dis Sci 43, 2237–2243 (1998). https://doi.org/10.1023/A:1026662521485

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026662521485

Search

Navigation