Neuromodulatory effects of atrial natriuretic factor are independent of guanylate cyclase in adrenergic neuronal pheochromocytoma cells.
This study tests the hypothesis that atrial natriuretic factor (ANF) and C-ANF(4-23)-NH2 (C-ANF) augment cGMP generation and inhibit both cAMP generation and depolarization-induced catecholamine release in nerve growth factor treated pheochromocytoma cells by a pertussis toxin (PTX)-sensitive mechanism. Synthetic rat ANF(99-126) and the clearance receptor antagonist C-ANF (10(-12)-10(-9) M) inhibited basal and 5 microM vasoactive intestinal peptide (VIP)-induced cAMP generation in a concentration-dependent manner. These actions of ANF and C-ANF were blocked by 12-18 h pretreatment with PTX (100 ng/ml), suggesting ANF receptor coupling to adenylate cyclase via an inhibitory guanine nucleotide-binding protein. Both ANF (10(-11)-10(-9) M) and C-ANF (10(-11)-10(-8) M) also inhibited K(+)-induced catecholamine release in a concentration-dependent manner. ANF (10(-11)-10(-8) M) increased cGMP generation in a concentration-dependent manner but C-ANF did not. The accumulation of cGMP in response to ANF was not altered by treatment with PTX. Therefore, PTX dissociated the increased concentrations of cGMP from the ANF-mediated depression of evoked catecholamine release. C-ANF also dissociated elevations in cGMP concentrations from an ANF-mediated attenuation of evoked catecholamine release. The results of this study indicate that ANF inhibits adrenergic neurotransmission independent of guanylate cyclase.
Drewett
J G
JG
Department of Pharmacology, University of Minnesota-Duluth School of Medicine.
Ziegler
R J
RJ
Trachte
G J
GJ
D037361:Adenylate Cyclase Toxin; D000310:Adrenal Gland Neoplasms / Q000473:pathology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004298:Dopamine / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D037342:Pertussis Toxin; D010673:Pheochromocytoma / Q000473:pathology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D010566:Virulence Factors, Bordetella; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D037342:Pertussis Toxin; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D011188:Potassium; D004298:Dopamine; D009638:Norepinephrine