Nitric oxide inhibits the initiation of cAMP pulsing in D. discoideum without altering receptor-activated adenylate cyclase.
We have previously demonstrated that nitric oxide (NO)-releasing compounds inhibit the differentiation and aggregation of D. discoideum cells (Tao et al., FEBS Lett. 314:49, 1992). In the present study, we demonstrate that treatment of intact cells with NO-releasing compounds inhibits their production of cAMP. This occurred even though the developmental expression of the known components necessary for proper cAMP signalling was unaffected. The inhibitory effects of NO-releasing compounds on cell aggregation were reversed by stimulating cells with pulses of cAMP. In response to an applied cAMP pulse, NO-treated cells displayed a normal signal relay response, indicating that receptor-activated adenylate cyclase activity was not inhibited by NO. This also argues that the processes of desensitization/resensitization occur normally in NO-treated cells. The data indicate that the developmental expression of the components of the chemotactic signalling occurs independently of cAMP production and that the activity of the adenylate cyclase may be regulated by cAMP/ cAMP-receptor independent pathway. These findings indicate both a new mechanism for the regulation of adenylate cyclase in D. discoideum and a novel means by which NO can function to alter cellular processes.
Tao
Y
Y
Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, MO 63104, USA.
Howlett
A
A
Klein
C
C
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002633:Chemotaxis / Q000187:drug effects; D000242:Cyclic AMP / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004023:Dictyostelium / Q000187:drug effects* / Q000502:physiology; D004789:Enzyme Activation; D005656:Fungal Proteins / Q000378:metabolism; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D010507:Periodicity; D011953:Receptors, Cyclic AMP / Q000187:drug effects* / Q000502:physiology; D015290:Second Messenger Systems / Q000187:drug effects*; D012636:Secretory Rate / Q000187:drug effects
D005656:Fungal Proteins; D011953:Receptors, Cyclic AMP; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases