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Inhibition of noradrenaline release by neuropeptide Y in mouse atria does not involve inhibition of adenylate cyclase or a pertussis toxin-susceptible G protein

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Summary

Neuropeptide Y (30–1000 nmol/1) significantly inhibited the fractional stimulation-induced outflow of radioactivity from mouse atria preincubated with [3H-noradrenaline. The inhibitory effect of neuropeptide Y was observed at all frequencies tested (2, 5 and 10 Hz) as well as after a-adrenoceptor blockade with phentolamine (1 µmol/l). A combination of 8-bromo adenosine cyclic-3′-5′-mono-phosphate (90 or 270 µmol/l) with the phosphodiesterase inhibitor 3-isobutyl-I-methylxanthine (100 µmol/l) was used to saturate maximally the adenylate cyclase system and these drug combinations significantly enhanced the stimulation-induced outflow of radioactivity. However, neuropeptide Y inhibited the stimulation-induced outflow in the presence of these drugs, suggesting that the inhibitory effect of neuropeptide Y was not due to decreasing endogenous cyclic AMP formation. Finally, atria from mice treated with pertussis toxin were used. In this case, the inhibitory effect of neuropeptide Y on the stimulation-induced outflow of radioactivity was still observed suggesting that inhibitory prejunctional neuropeptide Y receptors are not coupled to a pertussis toxin-susceptible G protein.

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References

  • Allen JM, Bloom SR (1986) Neuropeptide Y: a putative neurotransmitter. Neurochem Int 8:1–8

    Google Scholar 

  • A1lgaier C, Feuerstein TJ, Jackisch R, Hertting G (1985) Islet-activating protein (pertussis toxin) diminishes α2-adrenoceptor mediated effects on noradrenaline release. Naunyn-Schmiedeberg's Arch Pharmacol 331:235–239

    Google Scholar 

  • Boyer JL, Cardenas C, Posadas C, Garcia-Sainz JA (1983) Pertussis toxin induces tachycardia and impairs the increase in blood pressure produced by α2-adrenergic agonists. Life Sci 33:2627–2633

    Google Scholar 

  • Costa M, Majewski H (1988) Facilitation of noradrenaline release from sympathetic nerves through activation of ACTH receptors, \-adrenoceptors and angiotensin II receptors. Br J Pharmacol 95:993–1001

    Google Scholar 

  • Dahlöf C, Dahlöf P, Lundberg JM (1986) α-adrenoceptor-mediated inhibition of nerve stimulation-evoked release of neuropeptide Y (NPY)-like immunoreactivity in the pithed guinea-pig. Eur J Pharmacol 131:279–283

    Google Scholar 

  • Docherty JR (1988) Pertussis toxin and prejunctional α2-adrenoceptor in the rat heart and vas deferens. J Auton Pharmac 8:197–201

    Google Scholar 

  • Endoh M, Maruyama M, Iijima T (1985) Attenuation of muscarinic cholinergic inhibition by islet-activating protein in the heart. Am J Physiol 249:H309-H320

    Google Scholar 

  • Ewald DA, Sternweiss PC, Miller RJ (1988) Guanine nucleotide-binding protein Go-induced coupling of neuropeptide Y receptors to Ca2+ channels in sensory neurons. Proc Natl Acad Sci USA 85:3633–3637

    Google Scholar 

  • Fredholm BB, Lindgren E (1987) Effects of N-ethylmaleimide and forskolin on noradrenaline release from rat hippocampal slices. Evidence that prejunctional adenosine and α-receptors are linked to N-proteins but not to adenylate cyclase. Acta Physiol Scand 130:95–105

    Google Scholar 

  • Fredholm BB, Jansen I, Edvinsson L (1985) Neuropeptide Y is a potent inhibitor of cyclic AMP accumulation in feline blood vessels. Acta Physiol Scand 124:467–469

    Google Scholar 

  • Gu J, Polak JM, Allen JM, Huang WM, Sheppard MN, Tatemoto K, Bloom SR (1984) High concentrations of a novel peptide, neuropeptide Y, in the innvervation of the mouse and rat heart. J Histochem Cytochem 32:467–472

    Google Scholar 

  • Hackenthal E, Aktories K, Jakobs KH, Lang RE (1987) Neuropeptide Y inhibits renin release by a pertussis toxin-sensitive mechanism. Am J Physiol 252:F543-F550

    Google Scholar 

  • Häggblad J, Fredholm BB (1987) Adenosine and neuropeptide Y enhance α1-adrenoceptor-induced accumulation of inositol phosphates and attenuate forskolin-induced accumulation of cyclic AMP in rat vas deferens. Neurosci Lett 82:211–216

    Google Scholar 

  • Härfstrand A, Fredholm B, Fuxe K (1987) Inhibitory effects of neuropeptide Y on cyclic AMP accumulation in slices of the nucleus tractus solitarius region of the rat. Neurosci Lett 76:185–190

    Google Scholar 

  • Jakobs KH, Aktories K, Schultz G (1981) Inhibition of adenylate cyclase by hormones and neurotransmitters. Adv Cyclic Nucleotide Protein Phosphorylation Res 14:173–187

    Google Scholar 

  • Johnston H, Majewski H, Musgrave IF (1987) Involvement of cyclic nucleotides in prejunctional modulation of noradrenaline release in mouse atria. Br J Pharmacol 91:773–781

    Google Scholar 

  • Kassis S, Olasmaa M, Terenius L, Fishman PH (1987) Neuropeptide Y inhibits cardiac adenylate cyclase through a pertussis toxin-sensitive G protein. J Biol Chem 262:3429–3431

    Google Scholar 

  • Lundberg JM, Stjärne L (1984) Neuropeptide Y (NPY) depresses the secretion of 3H-noradrenaline and the contractile response evoked by field stimulation in rat vas deferens. Acta Physiol Scand 120:477–479

    Google Scholar 

  • Majewski H, Ishac E, Musgrave IF (1988) Intraneuronal mechanisms involved in the modulation of noradrenaline release through prejunctional receptors. In: Bevan JA, Majewski H, Maxwell RA, Story DF (eds) Vascular neuroeffector mechanisms. ICSU Press New York, pp 243–250

    Google Scholar 

  • Marley PB, Wilson JV, Habel H, Blaskett A (1985) Specific antibordetella pertussis activities in human blood examined by enzyme-linked immunoassay and biological assay. Dev Biol Stand 61:341–352

    Google Scholar 

  • Martin JM, Hunter DD, Nathanson NM (1985) Islet-activating protein inhibits physiological responses evoked by cardiac muscarinic acetylcholine receptors. Role of guanosine triphosphate binding proteins in regulation of potassium permeability. Biochemistry 24:7521–7525

    Google Scholar 

  • Miller RJ (1988) G proteins flex their muscles. Trends Neurosci 11:3–6

    Google Scholar 

  • Murayama T, Ui M (1983) Loss of the inhibitory function of the guanine nucleotide regulatory component of adenylate cyclase due to its ADP ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes. J Biol Chem 258:3319–3326

    Google Scholar 

  • Musgrave IF, Majewski H (1989) Effect of phorbol ester and pertussis toxin on the enhancement of noradrenaline release by angiotensin II in mouse atria. Br J Pharmacol 96:609–616

    Google Scholar 

  • Musgrave IF, Marley P, Majewski H (1987) Pertussis toxin does not attenuate α2-adrenoceptor mediated inhibition of noradrenaline release in mouse atria. Naunyn-Schmiedeberg's Arch Pharmacol 336:280–286

    Google Scholar 

  • Nabika T, Velletri PA, Lovenberg W, Beaven MA (1985) Increase in cytosolic calcium and phosphoinositide metabolism induced by angiotensin II and [arg] vasopressin in vascular smooth muscle. J Biol Chem 260:4661–4670

    Google Scholar 

  • Petrenko S, Olianas MC, Onali P, Gessa GL (1987) Neuropeptide Y inhibits forskolin-stimulated adenylate cyclase activity in rat hippocampus. Eur J Phrmacol 136:425–428

    Google Scholar 

  • Potter EK (1988) Neuropeptide Y as an autonomic neurotransmitter. Pharmacol Ther 37:251–273

    Google Scholar 

  • Reynolds EE, Yokota S (1988) Neuropeptide Y receptor-effector coupling mechanisms in cultured vascular smooth muscle cells. Biochem Biophys Res Commun 151:919–925

    Google Scholar 

  • Rudehill A, Sollevi A, Franco-Cereceda A, Lundberg JM (1986) Neuropeptide Y (NPY) and the pig heart: Release and coronary vasoconstrictor effects. Peptides 7:821–826

    Google Scholar 

  • Serfozo P, Bartfai T, Vizi ES (1986) Presynaptic effects of neuropeptide Y on [3H]-noradrenaline and [3H]-acetylcholine release. Regul Pept 16:117–123

    Google Scholar 

  • Shuntoh H, Taniyama K, Fukuzaki H, Tanaka C (1988) Inhibition of cyclic AMP of phorbol ester-potentiated norepinephirne release from guinea pig brain cortical synaptosomes. J Neurochem 51:1565–1572

    Google Scholar 

  • Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124

    Google Scholar 

  • Tatemoto K, Carlquist M, Mutt V (1982) Neuropeptide Y — a novel brain peptide with structural similarities to peptide YY and pancreatic polypeptide. Nature 296:659–660

    Google Scholar 

  • Wahlestedt C, Edvinsson L, Ekblad E, Håkanson R (1987) Effects of neuropeptide Y at sympathetic neuroeffector junctions: existence of Y1- and Y2-receptors. In: Nobin A, Owman C, Arneklo-Nobin B (eds) Neuronal messengers in vascular function. Elsevier, Amsterdam, pp 231–242

    Google Scholar 

  • Westfall TC, Carpentier S, Chen X, Beinfield MC, Naes L, Meldrum MJ (1987) Prejunctional and postjunctional effects of neuropeptide Y at the noradrenergic neuroeffector junction of the perfused mesenteric arterial bed of the rat. J Cardiovasc Pharmacol 10:716–722

    Google Scholar 

  • Westlind-Danielsson A, Urdén A, Abens J, Andell S, Bartfai T (1987) Neuropeptide Y receptors and the inhibition of adenylate cyclase in human frontal and temporal cortex. Neurosci Lett 74:237–242

    Google Scholar 

  • Wong-Dusting HK, Rand MJ (1988) Pre- and postjunctional effects of neuropeptide Y on the rabbit isolated ear artery. Clin Exp Pharmacol Physiol 15:411–418

    Google Scholar 

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  1. Department of Pharmacology, University of Melbourne, 3052, Parkville, Victoria, Australia

    Sylvain Foucart & Henryk Majewski

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  1. Sylvain Foucart
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  2. Henryk Majewski
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Foucart, S., Majewski, H. Inhibition of noradrenaline release by neuropeptide Y in mouse atria does not involve inhibition of adenylate cyclase or a pertussis toxin-susceptible G protein. Naunyn-Schmiedeberg's Arch. Pharmacol. 340, 658–665 (1989). https://doi.org/10.1007/BF00717741

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  • DOI: https://doi.org/10.1007/BF00717741

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