title: Adenosine-mediated inhibition of casein production by mouse mammary glands in culture.
abstract: The present study was carried out to examine whether activation of adenosine receptors by adenosine analogues will affect casein production by mouse mammary epithelial cells. The morphogenesis and functions of epithelial tissue in the mammary gland are influenced by their surrounding adipocytes. Adipocytes are known to release adenosine into the extracellular fluid which can modulate cyclic-AMP levels in surrounding cells through binding to their adenosine receptors. To examine a possible paracrine effect of adenosine, the modulation of casein production in mammary explant culture and mammary epithelial cell (MEC) culture by adenosine receptor agonists has been investigated. We have observed that activation of the A1-adenosine receptor subtype in mammary tissue by an adenosine analogue (-)N6-(R-phenyl-isopropyl)-adenosine (PIA) raised cAMP levels. PIA and another adenosine receptor agonist, isobutylmethylxanthine (IBMX), inhibited casein accumulation both in explants and in MEC cultures in the presence of lactogenic hormones, which suggests that PIA or adenosine can act directly on the epithelial cells. This inhibition does not appear to be caused by elevation of cAMP levels or phosphodiesterase activity. The inhibition of intracellular casein accumulation by PIA and IBMX in explant cultures can be reversed via treatment of pertussis toxin which is known to ADP-ribosylate GTP-binding G alpha i-proteins, indicating that a Gi-protein-dependent pathway may be involved in this inhibition. The results also suggest that local accumulation of adenosine in the extracellular fluids of mammary glands is likely to inhibit the lactogenic response of mammary epithelial cells.
authors.affiliation: Department of Anatomy, University of California, San Francisco 94143, USA.
authors.forename: Y K
authors.initials: YK
authors.lastname: Hom
authors.forename: G K
authors.initials: GK
authors.lastname: Bandyopadhyay
authors.forename: B K
authors.initials: BK
authors.lastname: Levay-Young
authors.forename: S
authors.initials: S
authors.lastname: Nandi
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D015153:Blotting, Western; D002364:Caseins / Q000096:biosynthesis*; D046508:Culture Techniques; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006854:Hydrocortisone / Q000494:pharmacology; D007288:Inosine / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011388:Prolactin / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D002364:Caseins; D010726:Phosphodiesterase Inhibitors; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D007288:Inosine; D011388:Prolactin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000241:Adenosine; D015232:Dinoprostone; D006854:Hydrocortisone; D004837:Epinephrine