HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Beta-adrenergic receptors in DMBA-induced rat mammary tumors: correlation with progesterone receptor and tumor growth.

Abstract
In order to gain further knowledge about the potential role of catecholamines in mammary carcinoma, we have used the potent beta-adrenergic antagonist cyanopindolol (CYP) as iodinated ligand to characterize beta-adrenergic receptors in membranes prepared from mammary tumors induced by dimethylbenz(a)anthracene (DMBA) administration in the rat. The binding of [125I]CYP to membrane preparations of DMBA-induced rat mammary tumors is rapid at room temperature, reaching half maximal specific binding at 30 min of incubation. Scatchard analysis of the data indicates that [125I]CYP binds to a single class of high affinity sites (114 +/- 2.1 fmoles/mg protein) at an apparent KD value of 38.0 +/- 0.3 pM. The order of potency of a series of agonists to compete for [125I]CYP binding is consistent with interaction with a beta 2-subtype receptor: zinterol greater than (-)isoproterenol greater than (-)epinephrine much greater than (-)norepinephrine. In addition, the potency of a series of specific beta 1 and beta 2 synthetic compounds to displace [125I]CYP in mammary tumors is similar to their potency in typical beta 2-adrenergic tissues. The binding of [125I]CYP to DMBA-induced rat mammary tumors shows a marked stereoselectivity, the (-)isomers of isoproterenol and propranolol being 150 and 80 times more potent, respectively, than their respective enantiomers. The autoradiographic localization of [125I]CYP performed on frozen sections revealed the presence of specific beta-adrenergic receptors in all the malignant cells. Spontaneous mammary tumors of aging (18-22 months) female rats have high levels of beta-adrenergic receptors. Castration decreased the concentration of [125I]CYP binding sites in DMBA-induced mammary tumors. A close correlation was observed between progressing, static, and regressing tumors after ovariectomy and beta-adrenergic receptor concentration. The presence of beta-adrenergic receptors in mammary tumors as well as the modulation of their level by ovarian hormones provides a mechanism for catecholaminergic influence in mammary cancer tissue.
AuthorsB Marchetti, P G Spinola, M Plante, P Poyet, N Folléa, G Pelletier, F Labrie
JournalBreast cancer research and treatment (Breast Cancer Res Treat) Vol. 13 Issue 3 Pg. 251-63 (Jul 1989) ISSN: 0167-6806 [Print] Netherlands
PMID2569332 (Publication Type: Journal Article)
Chemical References
  • Adrenergic beta-Antagonists
  • Catecholamines
  • Hormones
  • Iodine Radioisotopes
  • Receptors, Adrenergic, beta
  • Receptors, Progesterone
  • cyanopindolol
  • 9,10-Dimethyl-1,2-benzanthracene
  • Pindolol
Topics
  • 9,10-Dimethyl-1,2-benzanthracene
  • Adrenergic beta-Antagonists (metabolism)
  • Aging (physiology)
  • Animals
  • Catecholamines (metabolism)
  • Female
  • Hormones (metabolism)
  • Iodine Radioisotopes
  • Kinetics
  • Mammary Neoplasms, Experimental (chemically induced, metabolism, ultrastructure)
  • Neoplasm Regression, Spontaneous
  • Neoplasms, Hormone-Dependent (metabolism)
  • Ovariectomy
  • Pindolol (analogs & derivatives, metabolism)
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic, beta (metabolism)
  • Receptors, Progesterone (metabolism)
  • Substrate Specificity

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: