title: Characterization of adenosine receptors in bone. Studies on the effect of adenosine analogues on cyclic AMP formation and bone resorption in cultured mouse calvaria.
abstract: The effect of different adenosine analogues on cyclic AMP (cAMP) formation and bone resorption in cultured mouse calvarial bones was investigated. 5'-N-ethylcarboxamidoadenosine (NECA), R-N6-phenylisopropyl-adenosine (PIA), N6-cyclohexyl-adenosine (CHA) and 2-chloroadenosine all stimulated cyclic AMP formation with a threshold close to 1 mumol l-1); NECA was the most potent agonist. Theophylline (10, 100 mumol l-1) inhibited the cAMP accumulation induced by NECA and 2-chloroadenosine (30 and 300 mumol l-1), dose dependently. There was no inhibition of cAMP formation by PIA and CHA in forskolin-treated bone tissue. SQ 22, 536 and 2',5'-dideoxyadenosine (100 mumol l-1) both inhibited rolipram-stimulated cAMP formation. Cyclic AMP accumulation in isolated osteoblast-like cells from neonatal mouse calvarial bones was stimulated by NECA (10 and 100 mumol l-1) and 2-chloroadenosine (100 mumol l-1). 2-chloroadenosine (10 and 30 mumol l-1), but not NECA, PIA nor CHA, caused a dose-dependent stimulation of 45Ca release in both 48- and 120-h culture. The effect of 2-chloroadenosine on 45Ca release could not be antagonized by theophylline. Neither NECA, PIA, CHA nor 2-chloroadenosine could affect PTH-stimulated 45Ca release in short term cultures (6, 24 h). By contrast, stimulation of cAMP formation by forskolin or dibutyryl cAMP caused a rapid (6 h) inhibition of PTH-stimulated bone resorption. The results demonstrate functional A2 and P-site receptors in mouse calvaria and osteoblast-like cells, but no A1-receptor was detected. These adenosine receptors regulate cAMP, but are not intimately linked to bone resorption. The calcium mobilization induced by 2-chloroadenosine appears to be unrelated to adenosine receptors.
authors.affiliation: Department of Oral Pathology, University of Umeå, Sweden.
authors.forename: U H
authors.initials: UH
authors.lastname: Lerner
authors.forename: K
authors.initials: K
authors.lastname: Sahlberg
authors.forename: B B
authors.initials: BB
authors.lastname: Fredholm
mesh_terms: D015762:2-Chloroadenosine; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001862:Bone Resorption / Q000187:drug effects*; D001842:Bone and Bones / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D051379:Mice; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D011953:Receptors, Cyclic AMP / Q000187:drug effects*; D020889:Rolipram; D013806:Theophylline / Q000494:pharmacology
chemical_list: D011760:Pyrrolidinones; D011953:Receptors, Cyclic AMP; D015762:2-Chloroadenosine; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C027513:N(6)-cyclohexyladenosine; D013806:Theophylline; D000242:Cyclic AMP; D000225:Adenine; D020889:Rolipram; D000241:Adenosine