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.
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References
Abe Y, Tomita T (1968) Cable properties of smooth muscle. J Physiol (Lond) 196:87–100
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
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
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
Christophe J (1993) Type I receptors for PACAP a neuropeptide even more important than VIP? Biochim Biophys Acta 1154:183–199
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
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
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
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
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
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
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
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
Hoyle CHV (1992) Transmission: purines. In: Burnstock G, Hoyle CHV (eds) Autonomic neuroeffector mechanisms. Harwood Academic Publishers, Chur, pp 367–407
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Snedecor GW, Cochran WG (1967) Statistical methods, 6th edn. Iowa State University Press, Iowa
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
Tomita T (1972) Conductance change during the inhibitory potential in the guinea-pig taenia coli. J Physiol (Lond) 225:693–703
Vladimirova IA and Shuba MF (1978) Effect of strychnine, hydrastine, and apamine on synaptic transmission in smooth muscle cells. Neurophysiology 78:213–217
Voogd TE, Vansterkenburg ELM, Wilting J, Janssen LHM (1993) Recent research on the biological activity of suramin. Pharmacol Rev 45:177–203
Wieraszko A (1995) Facilitation of hippocampal potentials by suramin. J Neurochem 64:1097–1101
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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
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DOI: https://doi.org/10.1007/BF00169388