Abstract
1. In the isolated mesenteric vein of the dog, dipyridamole inhibited both the excitatory junction potential (e.j.p.) and the slow depolarization evoked by perivascular nerve stimulation, to 60-70% of control, with no change in the postjunctional membrane potential. These inhibitory actions of dipyridamole were not modified by 8-phenyltheophylline or phentolamine, suggesting that the inhibition did not involve either the actions of endogenous adenosine or the prejunctional alpha-autoregulation mechanism. 2. Dipyridamole did not produce any detectable effects on either the facilitation process of the e.j.ps or the postjunctional membrane depolarization produced by exogenously applied noradrenaline (NA). 3. Dipyridamole reduced the outflow of both the NA and the 3,4-dihydroxyphenylglycol (DOPEG) evoked by perivascular nerve stimulation to below 10% of control, the effect being much greater than that of exogenously applied adenosine (to about 90% of the control). 4. Exogenously-added NA was degraded by incubation with a segment of the vein. Dipyridamole itself produced degradation of NA and accelerated the NA-induced degradation. By contrast, pyrogallol, but not pargyline or imipramine, prevented the NA-induced degradation. 5. It is suggested that dipyridamole degrades NA directly, and also indirectly through activation of catechol-O-methyl transferase, with no alteration of the activity of monoamine oxidase or of the uptake mechanisms of NA into nerve terminals.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BUNAG R. D., DOUGLAS C. R., IMAI S., BERNE R. M. INFLUENCE OF A PYRIMIDOPYRIMIDINE DERIVATIVE ON DEAMINATION OF ADENOSINE BY BLOOD. Circ Res. 1964 Jul;15:83–88. doi: 10.1161/01.res.15.1.83. [DOI] [PubMed] [Google Scholar]
- Berne R. M., Knabb R. M., Ely S. W., Rubio R. Adenosine in the local regulation of blood flow: a brief overview. Fed Proc. 1983 Dec;42(15):3136–3142. [PubMed] [Google Scholar]
- Burnstock G., Kennedy C. A dual function for adenosine 5'-triphosphate in the regulation of vascular tone. Excitatory cotransmitter with noradrenaline from perivascular nerves and locally released inhibitory intravascular agent. Circ Res. 1986 Mar;58(3):319–330. doi: 10.1161/01.res.58.3.319. [DOI] [PubMed] [Google Scholar]
- Emmons P. R., Harrison M. J., Honour A. J., Mitchell J. R. Effect of a pyrimidopyrimidine derivative on thrombus formation in the rabbit. Nature. 1965 Oct 16;208(5007):255–257. doi: 10.1038/208255a0. [DOI] [PubMed] [Google Scholar]
- Enero M. A., Saidman B. Q. Possible feed-back inhibition of noradrenaline release by purine compounds. Naunyn Schmiedebergs Arch Pharmacol. 1977 Mar;297(1):39–46. doi: 10.1007/BF00508808. [DOI] [PubMed] [Google Scholar]
- Graefe K. H., Henseling M. Neuronal and extraneuronal uptake and metabolism of catecholamines. Gen Pharmacol. 1983;14(1):27–33. doi: 10.1016/0306-3623(83)90058-7. [DOI] [PubMed] [Google Scholar]
- Gresele P., Zoja C., Deckmyn H., Arnout J., Vermylen J., Verstraete M. Dipyridamole inhibits platelet aggregation in whole blood. Thromb Haemost. 1983 Dec 30;50(4):852–856. [PubMed] [Google Scholar]
- Griffith S. G., Meghji P., Moody C. J., Burnstock G. 8-phenyltheophylline: a potent P1-purinoceptor antagonist. Eur J Pharmacol. 1981 Oct 15;75(1):61–64. doi: 10.1016/0014-2999(81)90346-0. [DOI] [PubMed] [Google Scholar]
- Haslam R. J., Lynham J. A. Activation and inhibition of blood platelet adenylate cyclase by adenosine or by 2-chloroadenosine. Life Sci II. 1972 Dec 8;11(23):1143–1154. doi: 10.1016/0024-3205(72)90269-x. [DOI] [PubMed] [Google Scholar]
- Hedqvist P., Fredholm B. B. Effects of adenosine on adrenergic neurotransmission; prejunctional inhibition and postjunctional enhancement. Naunyn Schmiedebergs Arch Pharmacol. 1976 Jun;293(3):217–223. doi: 10.1007/BF00507344. [DOI] [PubMed] [Google Scholar]
- Katsuragi T., Su C. Augmentation by theophylline of [3H]purine release from vascular adrenergic nerves: evidence for presynaptic autoinhibition. J Pharmacol Exp Ther. 1982 Jan;220(1):152–156. [PubMed] [Google Scholar]
- Komori K., Nagao T., Zhang G. L., Ibengwe J. K., Fujioka M., Suzuki H. Bunazosin, an alpha 1-adrenoceptor blocker, differentially releases co-transmitters in dog mesenteric vessels. Eur J Pharmacol. 1989 May 2;164(1):111–120. doi: 10.1016/0014-2999(89)90237-9. [DOI] [PubMed] [Google Scholar]
- Kou K., Ibengwe J., Suzuki H. Effects of alpha-adrenoceptor antagonists on electrical and mechanical responses of the isolated dog mesenteric vein to perivascular nerve stimulation and exogenous noradrenaline. Naunyn Schmiedebergs Arch Pharmacol. 1984 May;326(1):7–13. doi: 10.1007/BF00518772. [DOI] [PubMed] [Google Scholar]
- Kuriyama H., Makita Y. The presynaptic regulation of noradrenaline release differs in mesenteric arteries of the rabbit and guinea-pig. J Physiol. 1984 Jun;351:379–396. doi: 10.1113/jphysiol.1984.sp015251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mishima S., Miyahara H., Suzuki H. Transmitter release modulated by alpha-adrenoceptor antagonists in the rabbit mesenteric artery: a comparison between noradrenaline outflow and electrical activity. Br J Pharmacol. 1984 Oct;83(2):537–547. doi: 10.1111/j.1476-5381.1984.tb16518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miyahara H., Suzuki H. Effects of tyramine on noradrenaline outflow and electrical responses induced by field stimulation in the perfused rabbit ear artery. Br J Pharmacol. 1985 Oct;86(2):405–416. doi: 10.1111/j.1476-5381.1985.tb08910.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moncada S., Korbut R. Dipyridamole and other phosphodiesterase inhibitors act as antithrombotic agents by potentiating endogenous prostacyclin. Lancet. 1978 Jun 17;1(8077):1286–1289. doi: 10.1016/s0140-6736(78)91269-2. [DOI] [PubMed] [Google Scholar]
- Oishi R., Mishima S., Kuriyama H. Determination of norepinephrine and its metabolites released from rat vas deferens using high-performance liquid chromatography with electrochemical detection. Life Sci. 1983 Feb 28;32(9):933–940. doi: 10.1016/0024-3205(83)90922-0. [DOI] [PubMed] [Google Scholar]
- Seki N., Suzuki H. Comparison of the prejunctional beta-adrenoceptor stimulating actions of adrenaline and isoprenaline in the dog mesenteric vein. Br J Pharmacol. 1989 Aug;97(4):1324–1330. doi: 10.1111/j.1476-5381.1989.tb12595.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Su C. Extracellular functions of nucleotides in heart and blood vessels. Annu Rev Physiol. 1985;47:665–676. doi: 10.1146/annurev.ph.47.030185.003313. [DOI] [PubMed] [Google Scholar]
- Suzuki H. Adrenergic transmission in the dog mesenteric vein and its modulation by alpha-adrenoceptor antagonists. Br J Pharmacol. 1984 Mar;81(3):479–489. doi: 10.1111/j.1476-5381.1984.tb10101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker L. A., Frölich J. C. Renal prostaglandins and leukotrienes. Rev Physiol Biochem Pharmacol. 1987;107:1–72. doi: 10.1007/BFb0027644. [DOI] [PubMed] [Google Scholar]
- Zhang G. L., Miyahara H., Suzuki H. Inhibitory actions of adenosine differ between ear and mesenteric arteries in the rabbit. Pflugers Arch. 1989 Oct;415(1):56–62. doi: 10.1007/BF00373141. [DOI] [PubMed] [Google Scholar]
