Abstract
Release of endogenous ATP elicited by electrical (neural) stimulation and exogenous agonists was studied in the rat isolated vas deferens. The aims were to dissect neural and postjunctional contributions to the nerve activity-evoked overflow of ATP and to clarify the role of transmitter receptors and calcium in postjunctional ATP release.
In tissues preincubated with [3H]-noradrenaline, electrical stimulation (100 pulses/10 Hz) elicited contraction and an overflow of tritium and ATP. Contractions as well as ATP overflow were reduced by prazosin 0.3 μM and even more so by prazosin 0.3 μM combined with suramin 300 μM. They were also reduced by nifedipine 10 μM and even more so by nifedipine 10 μM combined with ryanodine 20 μM (the additional effect of ryanodine on ATP overflow was not significant). In tissues not pretreated with [3H]-noradrenaline, exogenous noradrenaline 10 μM and α,β-methylene ATP 10 μM elicited contraction and an overflow of ATP. Responses to noradrenaline were blocked by prazosin 0.3 μM but not suramin 300 μM and were greatly reduced by nifedipine 10 μM and in Ca2+-free medium. Responses to α,β-methylene ATP were blocked by suramin 300 μM but not prazosin 0.3 μM were reduced by nifedipine 10 μM (effect on ATP overflow not significant) and were reduced even more in Ca2+-free medium. Neuropeptide Y 0.3 μM caused only very small contraction and ATP overflow. The electrically as well as the agonist-evoked ATP overflow correlated well with the contraction responses except in experiments with suramin which retarded the removal, by vas deferens tissue, of ATP from the medium.
Itsis concluded that the overflow of ATP from rat vas deferens elicited by electrical (neural) stimulation is at least 90% postjunctional, presumably smooth muscle, in origin. ATP is released from postjunctional cells as a consequence of both α1-adrenoceptor and P2-purinoceptor activation. Ca2+ is a second messenger in the postjunctional ATP release response; its major part enters through L-type channels. A “purely neural” overflow of ATP was not isolated under the conditions of the experiments.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bailey SJ, Hourani SMO (1994) Differential effects of suramin on P2-purinoceptors mediating contraction of the guinea-pig vas deferens and urinary bladder. Br J Pharmacol 112:219–225
Benham CD (1989) ATP-activated channels gate calcium entry in single smooth muscle cells dissociated from rabbit ear artery. J Physiol (Lond) 419:689–701
Bourreau JP, Zhang ZD, Low AM, Kwan CY, Daniel EE (1991) Ryanodine and the adrenergic, purinergic stimulation in the rat vas deferens smooth muscle: functional and radioligand binding studies. J Pharmacol Exp Ther 256:1063–1071
Bültmann R, Starke K (1994) Blockade by 4,4′-diisothiocyanatostilbene-2,2′-disulphonate (DIDS) of P2x-purinoceptors in rat vas deferens. Br J Pharmacol 112:690–694
Bültmann R, von Kügelgen I, Starke K (1993) Effects of nifedipine and ryanodine on adrenergic neurogenic contractions of rat vas deferens: evidence for a pulse-to-pulse change in Ca2+ sources. Br J Pharmacol 108:1062–1070
Bültmann R, Kurz AK, Starke K (1994a) α1-Adrenoceptors and calcium sources in adrenergic neurogenic contractions of rat vas deferens. Br J Pharmacol 111:151–158
Bültmann R, Trendelenburg M, Starke K (1994b) Blockade of P2X-purinoceptors by trypan blue in rat vas deferens. Br J Pharmacol (in press)
Driessen B, von Kügelgen I, Starke K (1993) Neural ATP release and its α2-adrenoceptor-mediated modulation in guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 348:358–366
Driessen B, von Kügelgen I, Starke K (1994) P1-purinoceptor-mediated modulation of neural noradrenaline and ATP release in guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 350:42–48
Fredholm BB, Fried G, Hedqvist P (1982) Origin of adenosine released from rat vas deferens by nerve stimulation. Eur J Pharmacol 79:233–243
Hedler L, Stamm G, Weitzell R, Starke K (1981) Functional characterization of central α-adrenoceptors by ychimbine diastereomers. Eur J Pharmacol 70:43–52
Hourani SMO, Chown JA (1989) The effects of some possible inhibitors of ectonucleotidases on the breakdown and pharmacological effects of ATP in the guinea-pig urinary bladder. Gen Pharmacol 20:413–416
Ishii R, Shinozuka K, Kobayashi Y, Hattori K, Hashimoto T, Takeuchi K (1993) Methoxamine enhances the release of endogenous noradrenaline from rabbit ear artery: possible involvement of ATP. Naunyn-Schmiedeberg's Arch Pharmacol 348:46–52
Kasakov L, Ellis J, Kirkpatrick K, Milner P, Burnstock G (1988) Direct evidence for concomitant release of noradrenaline, adenosine 5′-triphosphate and neuropeptide Y from sympathetic nerve supplying the guinea-pig vas deferens. J Anton Nerv Syst 22:75–82
Katsuragi T, Tokunaga T, Usune S, Furukawa T (1990) A possible coupling of postjunctional ATP release and transmitters' receptor stimulation in smooth muscles. Life Sci 46:1301–1307
Katsuragi T, Tokunaga T, Ogawa S, Soejima O, Sato C, Furukawa T (1991a) Existence of ATP-evoked ATP release system in smooth muscles. J Pharmacol Exp Ther 259:513–518
Katsuragi T, Tokunaga T, Usune S, Sato C, Furukawa T (1991b) Neurotransmitter-mediated ATP release from smooth muscles. In: Imai S, Nakazawa M (eds) Role of adenosine and adenine nucleotides in the biological system. Elsevier, Amsterdam, pp 407–414
Levitt B, Westfall DP (1982) Factors influencing the release of purines and norepinephrine in the rabbit portal vein. Blood Vessels 19:30–40
Lew MJ, White TD (1987) Release of endogenous ATP during sympathetic nerve stimulation. Br J Pharmacol 92:349–355
Limberger N, Trendelenburg AU, Starke K (1992) Pharmacological characterization of presynaptic α2-autoreceptors in rat submaxillary gland and heart atrium. Br J Pharmacol 107:246–255
Luchelli-Fortis MA, Fredholm BB, Langer SZ (1979) Release of radioactive purines from cat nictitating membrane labeled with 3H-adenine. Eur J Pharmacol 58:389–397
Lundberg JM, Terenius L, Hökfelt T, Martling CR, Tatemoto K, Mutt V, Polak J, Bloom S, Goldstein M (1982) Neuropeptide Y (NPY)-like immunoreactivity in peripheral noradrenergic neurons and effects of NPY on sympathetic function. Acta Physiol Scand 116:477–480
Mallard N, Marshall R, Sithers A, Spriggs B (1992) Suramin: a selective inhibitor of purinergic neurotransmission in rat isolated vas deferens. Eur J Pharmacol 220:1–10
Rump LC, von Kügelgen I (1994) A study of ATP as a sympathetic cotransmitter inhuman saphenous vein. Br J Pharmacol 111:65–72
Sedaa KO, Bjur RA, Shinozuka K, Westfall DP (1990) Nerve and drug-induced release of adenine nucleosides and nucleotides from rabbit aorta. J Pharmacol Exp Ther 252:1060–1067
Shinozuka K, Sedaa KO, Bjur RA, Westfall DP (1991) Participation by purines in the modulation of norepinephrine release by methoxamine. Eur J Pharmacol 192:431–434
Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124
Szabo B, Schultheiss A (1990) Desipramine inhibits sympathetic nerve activity in the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 342:469–476
Takeuchi K, Shinozuka K, Akimoto H, Ishii R, Hashimoto T (1994) Methoxamine-induced release of endogenous ATP from rabbit pulmonary artery. Eur J Pharmacol 254:287–290
Torres G, Bitran M, Huidobro-Toro JP (1992) Co-release of neuropeptide Y (NPY) and noradrenaline from the sympathetic nerve terminals supplying the rat vas deferens; influence of calcium and stimulation intensity. Neurosci Lett 148:39–42
Trendelenburg AU, Limberger N, Starke K (1993) Presynaptic α2-autoreceptors in brain cortex: α2d in the rat and αA in the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 348:35–45
Vizi ES, Burnstock G (1988) Origin of ATP release in the rat vas deferens: concomitant measurement of [3H]noradrenaline and [14C]ATP. Eur J Pharmacol 158:69–77
Vizi ES, Sperlágh B, Baranyi M (1992) Evidence that ATP, released from the postsynaptic site by noradrenaline, is involved in mechanical responses of guinea-pig vas deferens: cascade transmission. Neuroscience 50:455–465
von Kügelgen I, Starke K (1991) Release of noradrenaline and ATP by electrical stimulation and nicotine in guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 344:419–429
von Kügelgen I, Starke K (1994) Corelease of noradrenaline and ATP by brief pulse trains in guinea-pig vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 350:123–129
Westfall DP, Stitzel RE, Rowe JN (1978) The postjunctional effects and neural release of purine compounds in the guinea-pig vas deferens. Eur J Pharmacol 50:27–38
Westfall DP, Sedaa K, Bjur RA (1987) Release of endogenous ATP from rat caudal artery. Blood Vessels 24:125–127
Author information
Authors and Affiliations
Additional information
Correspondence to: R. Bültmann at the above address
Rights and permissions
About this article
Cite this article
Kurz, A.K., Bültmann, R., Driessen, B. et al. Release of ATP in rat vas deferens: origin and role of calcium. Naunyn-Schmiedeberg's Arch Pharmacol 350, 491–498 (1994). https://doi.org/10.1007/BF00173018
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00173018