Epidermal growth factor activation of rat parotid gland adenylate cyclase and mediation by a GTP-binding regulatory protein.
Injection of rats with a single dose of epidermal growth factor (EGF) or isoproterenol increased parotid gland acinar cell levels of cyclic AMP (cAMP) significantly above control basal concentrations (34, 177 and 11.5 pmol/g tissue/100 g body weight, respectively). Following a chronic regimen of isoproterenol (3 days), EGF, bovine galactosyltransferase (Gal Tase, EC 2.4.1.22) and isoproterenol increased cAMP levels, albeit to a lower level than observed for the single dose (21, 17 and 51 pmol, respectively). Using isolated parotid gland membranes, EGF and bovine galactosyltransferase also stimulated adenylate cyclase (EC 2.7.4.3) activity in a concentration-dependent manner. Introduction of the beta-adrenergic receptor antagonist propranolol blocked isoproterenol-stimulated adenylate cyclase activity and cAMP accumulation, but not that observed with EGF or the transferase treatment. Growth factor-stimulated adenylate cyclase activity required the presence of the guanosine triphosphate (GTP) analogue, guanyl-5'-imidodiphosphate (p[NH]ppG), while cAMP accumulation could additionally be blocked by introducing the GDP analog, guanosine 5'[beta-thio]diphosphate (GDP[S]). The ability of EGF to activate adenylate cyclase was not affected by pretreatment of acinar cell membranes with pertussis toxin, whereas pretreatment with cholera toxin eliminated EGF-stimulated cyclase activity. The experimental results presented here expand to the parotid gland our knowledge of the ability of EGF to stimulate the cAMP second messenger signalling pathway via a G-binding regulatory protein, by a mechanism independent of beta-adrenergic receptor activation.
Nakagawa
Y
Y
Department of Oral Biology, University of Florida, Gainesville 32610.
Gammichia
J
J
Purushotham
K R
KR
Schneyer
C A
CA
Humphreys-Beher
M G
MG
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005700:Galactosyltransferases / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D010306:Parotid Gland / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D015398:Signal Transduction / Q000187:drug effects
D004815:Epidermal Growth Factor; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D005700:Galactosyltransferases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol