title: Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in C-cells.
abstract: The effect of the adenosine A1 receptor activation on calcitonin secretion was studied in medullary thyroid carcinoma cells of the rat (rMTC 6-23). Calcitonin was determined by radioimmunoassay, intracellular cAMP by protein binding assay, intracellular calcium in fura-2 loaded single cells using microspectrofluorimetry, and calcium channel activity by patch clamp technique. The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)-10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M) stimulated cAMP formation and calcitonin secretion. These effects were partly abolished by pretreatment with pertussis toxin (PT) (100 ng/ml). PIA (10(-10)-10(-6) M) also suppressed extracellular calcium-stimulated calcitonin secretion, rises in intracellular calcium, and calcium channel currents. PT (100 ng/ml) pretreatment again partly abolished this inhibitory effect. The addition to the medium of adenosine deaminase (0.4 U/ml) stimulated calcitonin secretion. Our results suggest that in calcitonin-secreting cells A1 receptors couple to adenylate cyclase and calcium channels via PT-sensitive G proteins and thus inhibit calcitonin secretion. Adenosine seems to act as an autocrine/paracrine factor in calcitonin-secreting cells.
authors.affiliation: Abteilung Innere Medizin I, Universität Heidelberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Zink
authors.forename: H
authors.initials: H
authors.lastname: Scherübl
authors.forename: M
authors.initials: M
authors.lastname: Höflich
authors.forename: J
authors.initials: J
authors.lastname: Hescheler
authors.forename: F
authors.initials: F
authors.lastname: Raue
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002116:Calcitonin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000378:metabolism / Q000473:pathology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D005934:Glucagon / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D015220:Calcium Channels; D018047:Receptors, Purinergic P1; D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; D002116:Calcitonin; D005934:Glucagon; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D000241:Adenosine; D002118:Calcium