Skip to main content
SpringerLink
Log in

Evidence for two separate vasoconstriction-mediating nucleotide receptors, both distinct from the P2X-receptor, in rabbit basilar artery: a receptor for pyrimidine nucleotides and a receptor for purine nucleotides

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Uridine 5′-triphosphate- (UTP-) and adenosine 5′-triphosphate-(ATP) induced vasoconstriction was studied in the rabbit basilar artery. The arteries were incubated and perfused at a constant rate of flow. Vasoconstriction was measured as an increase in perfusion pressure.

Serotonin, histamine and noradrenaline caused concentration-dependent vasoconstriction, with potency decreasing in that order. Of the nucleotides tested, UTP, UDP, UMP, CTP, ATP, ADP, adenosine 5′-O-(3-thio)triphosphate (ATPγS), and β,γ-imido adenosine 5′-triphosphate (AMP-PNP) elicited concentration-dependent vasoconstriction, whereas AMP, 2-methylthio-ATP, α, β-methylene-ATP and β,γ-methylene-ATP up to 10−3 mol/l caused no or only a very small increase in perfusion pressure. The order of potency of the pyrimidine nucleotides was: UTP = UDP ≫ UMP = CTP; that of the purine nucleotides was: ATPγS > AMP-PNP > ATP > ADP > 2-methylthio-ATP = α, β-methylene-ATP = β,γ-methylene-ATP. The vasoconstrictor effects of UTP and ATP were not or only to a minor degree influenced by: phentolamine; a mixture of atropine, diphenhydramine and methysergide; indometacin; nordihydroguaiaretic acid; denervation by 6-hydroxydopamine; or mechanical removal of endothelium. Prolonged exposure to α,β-methylene-ATP elicited only a very small vasoconstriction and did not change the constrictor effects of UTP or ATP. Prolonged exposure to ATPγS elicited marked vasoconstriction; subsequently, responses to ATP were reduced whereas those to UTP were, if anything, slightly enhanced. Reactive blue 2 reduced neither the UTP- nor the ATP-induced vasoconstriction. ATP 10−3 mol/l elicited marked additional vasoconstriction after precontraction with UTP 10−3 mol/l, whereas UTP elicited only a very small additional vasoconstriction when its concentration was doubled from 10−3 to 2 × 10−3 mol/l.

It is concluded that, in the rabbit basilar artery, the vasoconstrictor response to UTP is mediated by a pyrimidine nucleotide receptor which is distinct from the P2-purinoceptor, and that the vasoconstrictor response to ATP is mediated by a P2-receptor which is distinct from the known P2-subtypes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aprigliano O, Hermsmeyer K (1976) In vitro denervation of the portal vein and caudal artery of the rat. J Pharmacol Exp Ther 198:568–577

    Google Scholar 

  • Araki H, Su C, Lee TJF (1982) Effect of superior cervical ganglionectomy on the sensitivity of rabbit ear artery and cerebral arteries of rabbit and cat to vasoactive agents. J Pharmacol Exp Ther 220:49–55

    Google Scholar 

  • Brown CM, Burnstock G (1981) The structural conformation of the polyphosphate chain of the ATP molecule is critical for its promotion of prostaglandin biosynthesis. Eur J Pharmacol 69:81–86

    Google Scholar 

  • Burnstock G, Kennedy C (1985) Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol 16:433–440

    Google Scholar 

  • Burnstock G, Warland JJI (1987) P2-purinoceptors of two subtypes in the rabbit mesenteric artery: reactive blue 2 selectively inhibits responses mediated via the P2Y- but not the P2X-purinoceptor. Br J Pharmacol 90:383–391

    Google Scholar 

  • Cockcroft S, Gomperts BD (1979) ATP induces nucleotide permeability in rat mast cells. Nature 279:541–542

    Google Scholar 

  • Cockcroft S, Gomperts BD (1980) The ATP4− receptor of rat mast cells. Biochem J 188:789–798

    Google Scholar 

  • Cusack NJ, Hourani SMO (1982) Competitive inhibition by adenosine 5′-triphosphate of the actions on human platelets of 2-chloroadenosine 5′-diphosphate, 2-azidoadenosine 5′-diphosphate and 2-methylthioadenosine 5′-diphosphate. Br J Pharmacol 77:329–333

    Google Scholar 

  • Fedan JS, Hogaboom GK, Westfall DP, O'Donnell JP (1982) Comparison of contractions of the smooth muscle of the guinea-pig vas deferens induced by ATP and related nucleotides. Eur J Pharmacol 81:193–204

    Google Scholar 

  • Goetz U, Da Prada M, Pletscher A (1971) Adenine-, guanine- and uridine-5′-phosphonucleotides in blood platelets and storage organelles of various species. J Pharmacol Exp Ther 178:210–215

    Google Scholar 

  • Gordon JL (1986) Extracellular ATP: effects, sources and fate. Biochem J 233:309–319

    Google Scholar 

  • Häussinger D, Stehle T, Gerok W (1987) Actions of extracellular UTP and ATP in perfused rat liver: a comparative study. Eur J Biochem 167:65–71

    Google Scholar 

  • Hardebo JE, Hanko J, Owman C (1983) Differences between human intra- and extracranial arteries in their reactivity to vasoactive agents. Gen Pharmacol 14:133–134

    Google Scholar 

  • Hardebo JE, Kåhrström J, Owman C (1987a) P1- and P2-purine receptors in brain circulation. Eur J Pharmacol 144:343–352

    Google Scholar 

  • Hardebo JE, Kåhrström J, Owman C, Salford LG (1987b) Endothelium-dependent relaxation by uridine tri- and diphosphate in isolated human pial vessels. Blood Vessels 24:150–155

    Google Scholar 

  • Jancar S, Schulz R, Krueger C, Cook DA (1987) Mechanisms of arachidonic acid-induced contractions of canine cerebral arteries. Eur J Pharmacol 136:345–352

    Google Scholar 

  • Kawai Y, Ohhashi T, Azuma T (1984) The mode of ATP-induced vasoconstriction in the canine internal carotid artery. Blood Vessels 21:98–104

    Google Scholar 

  • Keppens S, De Wulf H (1986) Characterization of the liver P2-purinoceptor involved in the activation of glycogen phosphorylase. Biochem J 240:367–371

    Google Scholar 

  • Kiwak KJ, Heros RC (1987) Cerebral vasospasm after subarachnoid hemorrhage. Trends Neurosci 10:89–92

    Google Scholar 

  • Lee TJF (1982) Cholinergic mechanism in the large cat cerebral artery. Circ Res 50:870–879

    Google Scholar 

  • Lukacsko P, Krell RD (1982) Response of the guinea-pig urinary bladder to purine and pyrimidine nucleotides. Eur J Pharmacol 80:401–406

    Google Scholar 

  • Meldrum LA, Burnstock G (1983) Evidence that ATP acts as a cotransmitter with noradrenaline in sympathetic nerves supplying the guinea-pig vas deferens. Eur J Pharmacol 92:161–163

    Google Scholar 

  • Muramatsu I, Kigoshi S (1987) Purinergic and non-purinergic innervation in the cerebral arteries of the dog. Br J Pharmacol 92:901–908

    Google Scholar 

  • Muramatsu I, Fujiwara M, Miura A, Shibata S (1980) Reactivity of isolated canine cerebral arteries to adenine nucleotides and adenosine. Pharmacology 21:198–205

    Google Scholar 

  • Needham L, Cusack NJ, Pearson JD, Gordon JL (1987) Characteristics of the P2 purinoceptor that mediates prostacyclin production by pig aortic endothelial cells. Eur J Pharmacol 134:199–209

    Google Scholar 

  • Rice WR, Singleton FM (1987) P2Y-purinoceptor regulation of surfactant secretion from rat isolated alveolar type II cells is associated with mobilization of intracellular calcium. Br J Pharmacol 91:833–838

    Google Scholar 

  • Saiag B, Milon D, Guelou MC, Van Den Driessche J, Rault B (1987) Pharmacological evidence for the existence of P2 purinoceptors different from “pyrimidinoceptors” on arterial and venous smooth muscle. Abstracts of the 10th International Congress of Pharmacology, Sydney 1987, P 949

  • Saito A, Lee TJF (1987) Serotonin as an alternative transmitter in sympathetic nerves of large cerebral arteries of the rabbit. Circ Res 60:220–228

    Google Scholar 

  • Seifert R, Burde R, Schultz G (1989) Activation of NADPH oxidase by purine and pyrimidine nucleotides involves G proteins and is potentiated by chemotactic peptides. Biochem J 259:813–819

    Google Scholar 

  • Shirasawa Y, White RP, Robertson JT (1983) Mechanisms of the contractile effect induced by uridine 5-triphosphate in canine cerebral arteries. Stroke 14:347–355

    Google Scholar 

  • Starke K, Peskar BA, Schumacher KA, Taube HD (1977) Bradykinin and postganglionic sympathetic transmission. Naunyn-Schmiedeberg's Arch Pharmacol 299:23–32

    Google Scholar 

  • Tahir J (1989) The effect of in vitro denervation on transmitter release in the rabbit basilar artery. Br J Pharmacol 96:123P

    Google Scholar 

  • Urquilla PR (1978) Prolonged contraction of isolated human and canine cerebral arteries induced by uridine 5′-triphosphate. Stroke 9:133–136

    Google Scholar 

  • Urquilla PR, Van Dyke K, Trush M (1978) Structure-activity relation of pyrimidine nucleotides and nucleoside in canine isolated cerebral vessels. J Pharm Pharmacol 30:189–190

    Google Scholar 

  • von Kügelgen I, Starke K (1985) Noradrenaline and adenosine triphosphate as co-transmitters of neurogenic vasoconstriction in rabbit mesenteric artery. J Physiol (Lond) 367:435–455

    Google Scholar 

  • von Kügelgen I, Starke K (1988) Vasoconstrictor effect of UTP and ATP in rabbit basilar artery. Naunyn-Schmiedeberg's Arch Pharmacol 337:R44

    Google Scholar 

  • von Kügelgen I, Häussinger D, Starke K (1987) Evidence for a vasoconstriction-mediating receptor for UTP, distinct from the P2 purinoceptor, in rabbit ear artery. Naunyn-Schmiedeberg's Arch Pharmacol 336:556–560

    Google Scholar 

  • von Kügelgen I, Schöffel E, Starke K (1989) Inhibition by nucleotides acting at presynaptic P2-receptors of sympathetic neuro-effector transmission in the mouse isolated vas deferens. Naunyn-Schmiedeberg's Arch Pharmacol 340:522–532

    Google Scholar 

  • Wallenstein S, Zucker CL, Fleiss JL (1980) Some statistical methods useful in circulation research. Circ Res 47:1–9

    Google Scholar 

  • Wiklund NP, Gustafsson LE (1988) Indications for P2-purinoceptor subtypes in guinea pig smooth muscle. Eur J Pharmacol 148:361–370

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmakologisches Institut, Hermann-Herder-Strasse 5, D-7800, Freiburg i. Br., Federal Republic of Germany

    Ivar von Kügelgen & Klaus Starke

Authors
  1. Ivar von Kügelgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Starke
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Send offprint requests to I. v. Kügelgen at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

von Kügelgen, I., Starke, K. Evidence for two separate vasoconstriction-mediating nucleotide receptors, both distinct from the P2X-receptor, in rabbit basilar artery: a receptor for pyrimidine nucleotides and a receptor for purine nucleotides. Naunyn-Schmiedeberg's Arch Pharmacol 341, 538–546 (1990). https://doi.org/10.1007/BF00171734

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00171734

Key words

Search

Navigation