Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Aug 15;270(1):137–140. doi: 10.1042/bj2700137

Alloxan inhibits ligand binding to adrenoceptors of vascular smooth muscle microsomes.

C Y Kwan 1, S Sipos 1, V Gaspar 1
PMCID: PMC1131689  PMID: 2396973

Abstract

We have examined the effects of alloxan on the binding of [3H]prazosin and [125I]monoiodocyanopindolol (ICYP) to plasma-membrane-enriched microsomes isolated from dog aortas and dog mesenteric arteries respectively. Preincubation of the vascular smooth muscle membranes with alloxan reduced the number of binding sites of the alpha- and beta-adrenoceptors in a concentration-dependent manner, whereas the affinity of the radioligands for the adrenoceptors was not affected by alloxan. Streptozotocin, which is also a diabetogenic agent like alloxan, had no effect on the radioligand binding to these adrenoceptors under similar experimental conditions. The inhibitory effects of alloxan on binding to beta-adrenoceptors were found to be highly pH-dependent. These results indicate that alloxan exerts adverse effects on cell membrane adrenoceptors in addition to those on the ion-transport function of vascular smooth muscle cell [Kwan (1988) Biochem. J. 254, 293-296], and also suggest that the primary site of action of alloxan is the plasma membrane.

Full text

PDF
137

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AVIADO D. M., Jr, SCHMIDT C. F. Pathogenesis of pulmonary edema by alloxan. Circ Res. 1957 Mar;5(2):180–186. doi: 10.1161/01.res.5.2.180. [DOI] [PubMed] [Google Scholar]
  2. Bobik A. Identification of alpha adrenoceptor subtypes in dog arteries by (3H) yohimbine and (3H) prazosin. Life Sci. 1982 Jan 18;30(3):219–228. doi: 10.1016/0024-3205(82)90502-1. [DOI] [PubMed] [Google Scholar]
  3. Frei B., Winterhalter K. H., Richter C. Mechanism of alloxan-induced calcium release from rat liver mitochondria. J Biol Chem. 1985 Jun 25;260(12):7394–7401. [PubMed] [Google Scholar]
  4. Heikkila R. E. Ascorbate-induced lipid peroxidation and the binding of [3H]dihydroalprenolol. Eur J Pharmacol. 1983 Sep 16;93(1-2):79–85. doi: 10.1016/0014-2999(83)90032-8. [DOI] [PubMed] [Google Scholar]
  5. Kwan C. Y., Beazley J. S. In vitro inhibition of calcium binding by alloxan and of calcium transport by isolated vascular smooth muscle microsomes. Can J Physiol Pharmacol. 1987 Nov;65(11):2346–2349. doi: 10.1139/y87-371. [DOI] [PubMed] [Google Scholar]
  6. Kwan C. Y., Beazley J. S. Mechanism of inhibition by alloxan of ATP-driven calcium transport by vascular smooth muscle microsomes. J Bioenerg Biomembr. 1988 Aug;20(4):517–531. doi: 10.1007/BF00762207. [DOI] [PubMed] [Google Scholar]
  7. Kwan C. Y., Osterroth A., Sipos S. N., Kosta P., Beazley J. S., Guan Y. Y., Daniel E. E. Interactions of saponin with microsomal membranes isolated from vascular smooth muscle. Arch Int Pharmacodyn Ther. 1988 Jan-Feb;291:55–67. [PubMed] [Google Scholar]
  8. Kwan C. Y., Sipos S. N., Osterroth A., Daniel E. E. Beta adrenoreceptor in vascular smooth muscle with special reference to subcellular localization and number of binding sites. J Pharmacol Exp Ther. 1987 Dec;243(3):1074–1081. [PubMed] [Google Scholar]
  9. Kwan C. Y. The plasma-membrane component is the primary site of action of alloxan on ATP-driven Ca2+ transport in vascular-muscle microsomal fractions. Biochem J. 1988 Aug 15;254(1):293–296. doi: 10.1042/bj2540293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kwan C. Y., Triggle C. R., Grover A. K., Lee R. M., Daniel E. E. An analytical approach to the preparation and characterization of subcellular membranes from canine mesenteric arteries. Prep Biochem. 1983;13(4):275–314. doi: 10.1080/00327488308068175. [DOI] [PubMed] [Google Scholar]
  11. Kwan C. Y., Triggle C. R., Grover A. K., Lee R. M., Daniel E. E. Membrane fractionation of canine aortic smooth muscle: subcellular distribution of calcium transport activity. J Mol Cell Cardiol. 1984 Aug;16(8):747–764. doi: 10.1016/s0022-2828(84)80658-6. [DOI] [PubMed] [Google Scholar]
  12. Malaisse W. J. Alloxan toxicity to the pancreatic B-cell. A new hypothesis. Biochem Pharmacol. 1982 Nov 15;31(22):3527–3534. doi: 10.1016/0006-2952(82)90571-8. [DOI] [PubMed] [Google Scholar]
  13. Nelson L., Boquist L. Effects of alloxan and streptozotocin on calcium transport in isolated mouse liver mitochondria. Cell Calcium. 1982 May;3(2):191–198. doi: 10.1016/0143-4160(82)90014-8. [DOI] [PubMed] [Google Scholar]
  14. Shi A. G., Kwan C. Y., Daniel E. E. Relation between density (maximum binding) of alpha adrenoceptor binding sites and contractile response in four canine vascular tissues. J Pharmacol Exp Ther. 1989 Sep;250(3):1119–1124. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES