title: Inhibition of atrial natriuretic peptide-induced cGMP accumulation by purinergic agonists in FRTL-5 thyroid cells. Involvement of both pertussis toxin-sensitive and insensitive mechanisms.
abstract: Extracellular ATP, N6-(L-2-phenylisopropyl)adenosine (PIA) and other purinergic agonists inhibited atrial natriuretic peptide (ANP)-induced cGMP accumulation in FRTL-5 thyroid cells. These agonists were functionally classified into three groups. Group 1 agonists represented by ATP inhibited the ANP action in association with phospholipase C activation in a partially islet-activating protein (IAP, pertussis toxin)-sensitive manner. Group 2 including GTP and 8-bromoadenosine 5'-triphosphate acted similarly to Group 1 except for total insensitivity of the former to IAP. The IAP-insensitive portion of Group 1 actions and the actions of Group 2 as well as of A23187, a Ca2+ ionophore which mimicked the Group 2 agonist actions, were almost completely inhibited by phosphodiesterase inhibitors such as M & B 22948 (2-O-propoxyphenyl-8-azapurin-6-one) and 3-isobutyl-1-methylxanthine. Group 3 including PIA and AMP did not affect phospholipase C, but inhibited the ANP performance in an IAP-sensitive fashion. This action of Group 3 and the IAP-sensitive portion of Group 1 actions were insensitive to the phosphodiesterase inhibitors. We conclude that ATP and other Group 1 agonists attenuated the ANP-induced cGMP accumulation by at least two mechanisms: 1) stimulation of cGMP hydrolysis via a phospholipase C-Ca2(+)-phosphodiesterase system and 2) inhibition of cGMP generation, probably by an IAP-sensitive G-protein-mediated inactivation of the ANP-receptor-coupled guanylate cyclase. Group 2 agonists stimulate only the first mechanisms, whereas Group 3 agonists prefer the second one.
authors.affiliation: Department of Physical Biochemistry, Gunma University Maebashi, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Okajima
authors.forename: Y
authors.initials: Y
authors.lastname: Kondo
mesh_terms: D000243:Adenosine Deaminase / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051381:Rats; D011983:Receptors, Purinergic / Q000502:physiology*; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013961:Thyroid Gland / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
chemical_list: D007295:Inositol Phosphates; D010726:Phosphodiesterase Inhibitors; D011983:Receptors, Purinergic; D010566:Virulence Factors, Bordetella; D010660:Phenylisopropyladenosine; D000001:Calcimycin; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D000243:Adenosine Deaminase; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D009638:Norepinephrine