Summary
Experiments were designed to evaluate the effect of cyclic AMP on the electrically-induced release of noradrenaline from vascular sympathetic nerve terminals. The possible implication of the inhibition of adenylate cyclase in the negative feed-back control by prejunctional α2-adrenoceptors of neurotransmitter release was also investigated. Rat isolated tail arteries were preincubated with [3H]-noradrenaline; the preparations were subsequently perfused/superfused with [3H]-noradrenaline-free medium and their perivascular nerves were field stimulated with 24 pulses at 0.4 Hz (0.3 ms, 200 mA). 2 compounds known to enhance the intracellular concentration of cyclic AMP, namely the membrane permeant analogue 8-Br-cAMP (10–300 µmol/l) and forskolin (0.3–10 µmol/l), an activator of adenylate cyclase, concentration-dependently enhanced the stimulation-evoked tritium overflow. The 1,9-dideoxy derivative of forskolin, which does not stimulate adenylate cyclase, was ineffective. Exposure to the cyclic AMP phosphodiesterase inhibitor rolipram 30 µmol/l produced a moderate increase (about 20%) in tritium overflow. However, in the presence of rolipram the facilitatory effect of forskolin was significantly more pronounced than in its absence. Whereas 8-Br-cAMP produced a slight concentration-dependent enhancement of the stimulation-induced vasoconstriction, forskolin and rolipram depressed it.
The α2-adrenoceptor agonist B-HT 933 (3–30 µmol/l) concentration-dependently inhibited the tritium overflow. The effect of B-HT 933 30 µmol/l was slightly, but significantly reduced in the presence of 8-Br-cAMP 100 and 300 µmol/l, but was not changed in the presence of forskolin 3 µmol/l The facilitatory effect of rauwolscine 1 µmol/l was enhanced in the presence of 8-Br-cAMP 100 µmol/l. During perfusion with 8-Br-cAMP 100 µmol/l, the current strength and frequency were decreased to 150 mA and 0.2 Hz, respectively in order to obtain similar amounts of tritium overflow to those observed in the absence of the cyclic AMP analogue with the initial stimulation parameters. Under these conditions, the inhibition of the overflow by B-HT 933 30 µmol/l and the facilitation by the α2-adrenoceptor antagonist rauwolscine 1 µmol/l were unaltered as compared to controls under initial stimulation conditions.
It is concluded that, in the rat tail artery, the terminals of perivascular sympathetic nerves are endowed with an adenylate cyclase system. Cyclic AMP is able to modulate noradrenaline release, but does not appear to play a role in the initiation of the release process itself. In addition, the results do not support the hypothesis that prejunctional α2-adrenoceptors depress noradrenaline release through the inhibition of adenylate cyclase.
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References
Alberts P, Ögren VR, Sellström AI (1985) Role of adenosine 3′,5′cyclic monophosphate in adrenoceptor-mediated control of 3H-noradrenaline secretion in guinea-pig ileum myenteric nerve terminals. Naunyn-Schmiedeberg's Arch Pharmacol 330:114–120
Andén NE, Golembiowska-Nikitin K, Thornström U (1982) Selective stimulation of dopamine and noradrenaline autoreceptors by B-HT 920 and B-HT 933, respectively. Naunyn-Schmiedeberg's Arch Pharmacol 321:100–104
Bao JX, Eriksson IE, Stjärne L (1989) Neurogenic contractions in the rat tail artery of normotensive rats are mediated by noradrenaline and ATP via post-junctional α1- and α2-adrenoceptors and P2x-purinoceptors. Acta Physiol Scand 136:139–140
Blaustein MP (1979) The role of calcium in catecholamine release from adrenergic nerve terminals. In: Paton DM (ed) The release of catecholamines from adrenergic neurons. Pergamon, Oxford, pp 39–58
Brown AM, Birnbaumer L (1988) Direct G protein gating of ion channels. Am J Physiol 245:H401-H410
Bucher B, Bettermann R, Illes P (1987) Plasma concentration and vascular effect of β-endorphin in spontaneously hypertensive and Wistar Kyoto rats. Naunyn-Schmiedeberg's Arch Pharmacol 335:428–432
Cichini G, Singer EA (1987) B-HT 920, B-HT 933, and B-HT 958: presynaptic effects on electrically evoked 3H-noradrenaline release from slices of rat brain cortex and hypothalamus. Naunyn-Schmiedeberg's Arch Pharmacol 335:613–617
Cubeddu L, Barnes E, Weiner N (1975) Release of norepinephrine and dopamine β-hydroxylase by nerve stimulation. IV. An evaluation of a role for cyclic adenosine monophosphate. J Pharmacol Exp Ther 193:105–127
Encina JL, Hartung F, Tripathi O, Nawrath H (1988) Analysis of the hyperpolarizing effects of forskolin in guinea-pig atrial heart muscle. Naunyn-Schmiedeberg's Arch Pharmacol 337:435–439
Ertl R, Nawrath H (1989) Cyclic AMP-independent membrane effects of forskolin in atrial and ventricular heart and aortic smooth muscle preparations from guinea pigs. Naunyn-Schmiedeberg's Arch Pharmacol Suppl 339:R52
Exton JH (1982) Molecular mechanisms involved in α-adrenergic responses. Trends Pharmacol Sci 3:111–115
Göthert M, Hentrich F (1984) Role of cAMP for regulation of impulse-evoked noradrenaline release from rabbit pulmonary artery and its possible relationship to presynaptic ACTH receptors. Naunyn-Schmiedeberg's Arch Pharmacol 328:127–134
Hentrich F, Göthert M, Greschuchna D (1985) Involvement of cAMP in modulation of noradrenaline release in the human pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 330:245–247
Hoshi T, Garber SS, Aldrich RW (1988) Effect of forskolin on voltage-gated K+ channels is independent of adenylate cyclase activation. Science 240:1652–1655
Illes P (1986) Mechanisms of receptor-mediated modulation of transmitter release in noradrenergic, cholinergic and sensory neurones. Neuroscience 17:909–928
Illes P, Bettermann R, Brod I, Bucher B (1987) β-Endorphin-sensitive opioid receptors in the rat tail artery. Naunyn-Schmiedeberg's Arch Pharmacol 335:420–427
Jakobs KH, Aktories K, Schultz G (1981) Inhibition of adenylate cyclase by hormones and neurotransmitters. Adv Cyclic Nucleotide Res 14:173–186
Johnston H, Majewski H (1986) Prejunctional β-adrenoceptors in rabbit pulmonary artery and mouse atria: effect of α-adrenoceptor blockade and phosphodiesterase inhibition. Br J Pharmacol 87:553–562
Johnston H, Majewski H, Musgrave IF (1987) Involvement of nucleotides in prejunctional modulation of noradrenaline release in mouse atria. Br J Pharmacol 91:773–781
Langer SZ (1981) Presynaptic regulation of the release of catecholamines. Pharmacol Rev 32:337–362
Limberger N, Späth L, Starke K (1988) Presynaptic α2-adrenoceptor, opioid κ-receptor and adenosine A1-receptor interactions on noradrenaline release in rabbit brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 338:53–61
Lugnier C, Schoeffter P, Le Bee A, Strouthou E, Stoclet JC (1986) Selective inhibition of cyclic nucleotide phosphodiesterases of human, bovine and rat aorta. Biochem Pharmacol 35:1743–1751
Markstein R, Digges K, Marshall NR, Starke K (1984) Forskolin and the release of noradrenaline in cerebrocortical slices. Naunyn-Schmiedeberg's Arch Pharmacol 325:17–24
Mattera R, Graziano MP, Yatani A, Zhou Z, Graf R, Codina J, Birnbaumer L, Gilman AG, Brown AM (1989) Splice variants of the a subunit of the G protein Gs activate both adenylyl cyclase and calcium channels. Science 243:804–807
Mulder AH, Schoffelmeer ANM (1985) Catecholamine and opioid receptors, presynaptic inhibition of CNS neurotransmitter release, and adenylate cyclase. Adv Cycl Nucleotide Protein Phosphoryl Res 19:273–286
Muller MJ, Baer HP (1983) Relaxant effects of forskolin in smooth muscle. Role of cyclic AMP. Naunyn-Schmiedeberg's Arch Pharmacol 322:78–82
Neer EJ, Clapham DE (1988) Roles of G protein subunits in transmembrane signalling. Nature 333:129–134
Rodbell M (1980) The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284:17–22
Schlicker E, Fink K, Classen K, Göthert M (1987) Facilitation of serotonin (5-HT) release in the rat brain cortex by cAMP and probable inhibition of adenylate cyclase in 5-HT nerve terminals by presynaptic α2-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 336:251–256
Schoffelmeer ANM, Mulder AH (1983) 3H-Noradrenaline release from rat neocortical slices in the absence of extracellular Ca2+ and its presynaptic alpha2-adrenergic modulation. A study on the possible role of cyclic AMP. Naunyn-Schmiedeberg's Arch Pharmacol 323:188–192
Schoffelmeer ANM, Hogenboom F, Mulder AH (1985) Evidence for a presynaptic adenylate cyclase system facilitating [3H]-norepinephrine release from rat brain neocortex slices and synaptosomes. J Neurosci 5:2685–2689
Schoffelmeer ANM, Wierenga EA, Mulder AH (1986) Role of adenylate cyclase in presynaptic α2-adrenoceptor- and µ-opioid receptor-mediated inhibition of [3H]noradrenaline release from rat brain cortex slices. J Neurochem 46:1711–1717
Schwabe U, Miyake M, Ohga Y, Daly JW (1976) 4-(3-Cyclopentyloxy-4-methoxy-phenyl)-2-pyrrolidone (ZK 62711): A potent inhibitor of cyclic AMP-phosphodiesterases in homogenates and tissue slices from rat brain. Mol Pharmacol 12:900–910
Seamon KB, Daly JW (1983) Forskolin, cyclic AMP and cellular physiology. Trends Pharmacol Sci 4:120–123
Seamon KB, Daly JW (1986) Forskolin: Its biological and chemical properties. Adv Cyclic Nucleotide Protein Phosphorylation Res 20:1–150
Sneddon P, Burnstock G (1984) ATP as a co-transmitter in rat tail artery. Eur J Pharmacol 106:149–152
Starke K (1981) Presynaptic receptors. Ann Rev Pharmacol Toxicol 21:7–30
Starke K (1987) Presynaptic α-autoreceptors. Rev Physiol Pharmacol 107:73–146
Stjärne L, Bartfai T, Alberts P (1979) The influence of 8-Br 3′,5′cyclic nucleotide analogs and of inhibitors of 3′,5′-cyclic nucleotide phosphodiesterase, on noradrenaline secretion and neuromuscular transmission in guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 308:99–105
Weber HD (1989) Presynaptic α2-adrenoceptors at the terminals of perivascular sympathetic nerves are coupled to an N-ethylmaleimide-sensitive G-protein. Naunyn-Schmiedeberg's Arch Pharmacol Suppl 339:R35
Weitzell R, Tanaka T, Starke K (1979) Pre- and postsynaptic effects of yohimbine stereoisomers on noradrenergic transmission in the pulmonary artery of the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 308:127–136
Wemer J, Schoffelmeer ANM, Mulder AH (1982) Effects of cyclic AMP analogues and phosphodiesterase inhibitors on K+-induced [3H]noradrenaline release from rat brain slices and on its presynaptic a-adrenergic modulation. J Neurochem 39:349–356
Wilffert B, Smit G, de Jonge A, Thoolen MJMC, Timmermans PBMWM, van Zwieten PA (1984) Inhibitory dopamine receptors on sympathetic neurons innervating the cardiovascular system of the pithed rat. Characterization and role in relation to presynaptic α2-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 326:91–98
Wooten GF, Thoa NB, Kopin IJ, Axelrod J (1973) Enhanced release of dopamine β-hydroxylase and norepinephrine from sympathetic nerves by dibutyryl cyclic adenosine 3′,5′-monophosphate and theophylline. Mol Pharmacol 9:178–183
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Bucher, B., Pain, L., Stoclet, J.C. et al. Role of cyclic AMP in the prejunctional α2-adrenoceptor modulation of noradrenaline release from the rat tail artery. Naunyn-Schmiedeberg's Arch Pharmacol 342, 640–649 (1990). https://doi.org/10.1007/BF00175706
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DOI: https://doi.org/10.1007/BF00175706