Skip to main content
SpringerLink
Log in

Electrophysiological analysis of the actions of pituitary adenylyl cyclase activating peptide in the taenia of the guinea-pig caecum

  • Original Article
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The actions of pituitary adenylyl cyclase activating peptide (PACAP) on membrane potential and conductance were investigated in the taenia of the guinea-pig caecum. The possible role of PACAP in inhibitory transmission was also investigated. Membrane potentials of smooth muscle cells were measured by intracellular microelectrodes, in the presence of hyoscine and nifidepine (both 10−6M). To determine conductance changes, current was passed from external plate electrodes using the technique of Abe and Tomita (1968). PACAP-27 caused a concentration dependent hyperpolarization of the muscle with a maximum of 12–15 mV at 10−6M. The hyperpolarization caused by PACAP was associated with a substantial increase in membrane conductance. The hyperpolarization was abolished by apamin (10−6M), a blocker of small conductance, calcium-dependent, potassium channels, and was reduced to about 50% by suramin (10−4M), which is an antagonist of P2 receptors for purines. The hyperpolarization was not reduced by tetrodotoxin (2 × 10−6M), suggesting PACAP acts directly on the muscle. With continued exposure to PACAP, the hyperpolarization decayed back to resting membrane potential after several minutes, possibly due to receptor desensitization. Inhibitory junction potentials (IJPs) were markedly reduced in amplitude in the period of presumed receptor desensitization to PACAP, were abolished by tetrodotoxin, but were not affected by suramin. Apamin abolished the UP and revealed a small excitatory junction potential. This study implies that PACAP released from nerve fibres in the taenia caeci hyperpolarizes the muscle via an opening of apamin-sensitive potassium channels. The action is probably through type I PACAP receptors.

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

  • Abe Y, Tomita T (1968) Cable properties of smooth muscle. J Physiol (Lond) 196:87–100

    Google Scholar 

  • Bennett MR (1966) A model of the membrane of smooth muscle cells of the guinea-pig taenia coli muscle during transmission from inhibitory and excitatory nerves. Nature (Loud) 211:1149–1152

    Google Scholar 

  • Bennett MR, Burnstock G, Holman ME (1963) The effect of potassium chloride ions in the inhibitory potential recorded in the guinea-pig taenia coli. J Physiol 169:33–34P

    Google Scholar 

  • Bennett MR, Burnstock G, Holman ME (1966) Transmission from intramural inhibitory nerves to the smooth muscle of the guineapig taenia coli. J Physiol (Lond) 182:541–558

    Google Scholar 

  • Christophe J (1993) Type I receptors for PACAP a neuropeptide even more important than VIP? Biochim Biophys Acta 1154:183–199

    Google Scholar 

  • Costa M, Furness JB, Humphreys CMS (1986) Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract. Naunyn-Schmiedeberg's Arch Pharmacol 332:79–88

    Google Scholar 

  • Furness JB, Pompolo S, Shuttleworth CWR, Burleigh DE (1992) Light- and electron-microscopic immunochemical analysis of nerve fibre types innervating the taenia of the guinea-pig caecum. Cell Tissue Res 270:125–137

    Google Scholar 

  • Furness JB, Young HM, Pompolo S, Bornstein JC, Kunze WAA, McConalogue K (1995) Plurichemical transmission and chemical coding of neurons in the digestive tract. Gastroenterology 108:554–563

    Google Scholar 

  • Grider JR, Cable MB, Bitar KN, Said SI, Makhlouf GM (1985) Vasoactive intestinal polypeptide: relaxant neurotransmitter in taenia coli of the guinea pig. Gastroenterology 89:36–42

    Google Scholar 

  • Grider JR, Bitar KN, Makhlouf GM (1987) Identification of muscarinic M2 receptors on single muscle cells of the human and guinea pig intestine. Gastroenterology 93:951–957

    Google Scholar 

  • Grider JR, Murthy KS, Jin J-G, Makhlouf GM (1992) Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release. Am J Physiol 262:G774-G778

    Google Scholar 

  • Grider JR, Katsoulis S, Schmidt WE, Jin J-G (1994) Regulation of the descending relaxation phase of intestinal peristalsis by PACAP. J Auton Nerv Syst 50:151–159

    Google Scholar 

  • Hills JM, Collis CS, Burnstock G (1983) The effects of vasoactive intestinal polypeptide on. the electrical activity of guinea-pig smooth muscle. Eur J Pharmacol 88:371–376

    Google Scholar 

  • Hoyle CHV (1992) Transmission: purines. In: Burnstock G, Hoyle CHV (eds) Autonomic neuroeffector mechanisms. Harwood Academic Publishers, Chur, pp 367–407

    Google Scholar 

  • Hoyle CHV, Knight GE, Burnstock G (1990) Suramin antagonizes responses to P2-purinoceptor agonists and purinergic nerve stimulation in the guinea-pig urinary bladder and taenia coli. Br J Pharmac 99:617–621

    Google Scholar 

  • Jin J-G, Murthy KS, Grider JR, Makhlouf GM (1993) Activation of distinct cAMP- and cGMP- dependent pathways by relaxant agents in isolated gastric muscle cells. Am J Physiol 264:G470-G477

    Google Scholar 

  • Jin J-G, Katsoulis S, Schmidt WE, Grider JR (1994) Inhibitory transmission in tenia coli mediated by distinct vasoactive intestinal peptide and apamin-sensitive pituitary adenylate cyclase activating peptide receptors. J Pharmacol Exp Ther 270:433–439

    Google Scholar 

  • Katsoulis S, Clemens A, Schwörer H, Creutzfeldt W, Schmidt W (1993) Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent relaxant of the rat ileum. Peptides 14:587–592

    Google Scholar 

  • Köves K, Arimura A, Vigh S, Somogyvari-Vigh A, Miller J (1993) Immunohistochemical localization of PACAP in the ovine digestive system. Peptides 14:449–455

    Google Scholar 

  • Li CG, Rand MJ (1990) Nitric oxide and vasoactive intestinal polypeptide mediate non-adrenergic, non-cholinergic inhibitory transmission to smooth muscle of the rat gastric fundus. Eur J Pharmacol 191:303–309

    Google Scholar 

  • MacKenzie I and Burnstock G (1980) Evidence against vasoactive intestinal polypeptide being the non-adrenergic, non-cholinergic inhibitory transmitter released from nerves supplying the smooth muscle of the guinea-pig taenia coli. Eur J Pharmacol 67:255–264

    Google Scholar 

  • McConalogue K, Furness JB, Murphy R, Vremec MA, Marley PD (1993) Actions of possible enteric transmitters on adenylyl and guanylyl cyclases in the guinea-pig taenia coli. Proceedings of the Australian Neuroscience Society 4:182

    Google Scholar 

  • McConalogue K, Furness JB, Vremec MA, Holst JJ, Tornøe K, Marley PD (1995) 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 50:311–322

    Google Scholar 

  • Nakazawa K, Inoue K, Ito K, Koizumi S, Inoue K (1995) Inhibition by suramin and reactive blue 2 of GABA and glutamate receptor channels in rat hippocampal neurons. Naunyn-Schmiedeberg's Arch Pharmacol 351:202–208

    Google Scholar 

  • Piotrowski W, Simon MC, Brennan L (1993) Effects of Nw-nitro-l-arginine and methylene blue on non-adrenergic, non-cholinergic responses of isolated guinea-pig taenia caeci. Br J Pharmac 110:157P

    Google Scholar 

  • Portbury AL, McConalogue K, Furness JB, Young HM (1995) Distribution of pituitary adenylyl cyclase activating peptide (PACAP) immunoreactivity in neurons of the guinea-pig digestive tract and their projections in the ileum and colon. Cell Tissue Res 279:385–392

    Google Scholar 

  • Rand MJ (1992) Nitrergic transmission: Nitric oxide as a mediator of non-adrenergic, non-cholinergic neuro-effector transmission. Clin Exp Pharmacol Physiol 19:147–169

    Google Scholar 

  • Rand MJ and Li CG (1990) Nitric oxide mediates non-adrenergic non-cholinergic relaxation in some neuroeffector systems: examples of nitrergic transmission. Eur J Pharmacol 183:1144

    Google Scholar 

  • Schwörer H, Katsoulis S, Creutzfeldt W, Schmidt WE (1992) Pituitary adenylate cyclase activating peptide, a novel VIP-like gut-brain peptide, relaxes the guinea-pig taenia caeci via apamin-sensitivite potassium channels. Naunyn-Schmiedeberg's Arch Pharmacol 346:511–514

    Google Scholar 

  • Schwörer H, Clemens A, Katsoulis S, Kohler H, Creutzfeldt W, Schmidt WE (1993) Pituitary adenylate cyclase-activating peptide is a potent modulator of human colonic motility. Scand J Gastroenterol 28:625–632

    Google Scholar 

  • Shen Z, Larsson LT, Malmfors G, Absood A, Häkanson R, Sundler F (1992) A novel neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP), in human intestine: evidence for reduced content in Hirschsprung's disease. Cell Tissue Res 269:369–374

    Google Scholar 

  • Sjoqvist A, Fahrenkrug J, Jodal M, Lundgren O (1983) Effect of apamin on release of vasoactive intestinal polypeptide (VIP) from the cat intestines. Acta Physiol Scand 119:69–76

    Google Scholar 

  • Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. Iowa State University Press, Iowa

    Google Scholar 

  • Sundler F, Ekblad E, Absood A, Håkanson R, Köves K, Arimura A (1992) Pituitary adenylate cyclase activating peptide: a novel vasoactive intestinal peptide-like neuropeptide in the gut. Neuroscience 46:439–454

    Google Scholar 

  • Tomita T (1972) Conductance change during the inhibitory potential in the guinea-pig taenia coli. J Physiol (Lond) 225:693–703

    Google Scholar 

  • Vladimirova IA and Shuba MF (1978) Effect of strychnine, hydrastine, and apamine on synaptic transmission in smooth muscle cells. Neurophysiology 78:213–217

    Google Scholar 

  • Voogd TE, Vansterkenburg ELM, Wilting J, Janssen LHM (1993) Recent research on the biological activity of suramin. Pharmacol Rev 45:177–203

    Google Scholar 

  • Wieraszko A (1995) Facilitation of hippocampal potentials by suramin. J Neurochem 64:1097–1101

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy and Cell Biology, University of Melbourne, 3052, Parkville, Victoria, Australia

    K. McConalogue & J. B. Furness

  2. Department of Physiology, Monash University, 3168, Clayton, Victoria, Australia

    D. J. K. Lyster

Authors
  1. K. McConalogue
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. B. Furness
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. J. K. Lyster
    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

McConalogue, K., Furness, J.B. & Lyster, D.J.K. Electrophysiological analysis of the actions of pituitary adenylyl cyclase activating peptide in the taenia of the guinea-pig caecum. Naunyn-Schmiedeberg's Arch Pharmacol 352, 538–544 (1995). https://doi.org/10.1007/BF00169388

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00169388

Key words

Search

Navigation