ANP relaxes bovine tracheal smooth muscle and increases cGMP.
Effects of atrial natriuretic peptides (ANP) on the tension, content of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) and activity of particulate and soluble forms of guanylate cyclase were examined in bovine tracheal smooth muscle. Atrial natriuretic factor (ANF), atriopeptin II, and atriopeptin III were found to induce relaxation of tracheal smooth muscle precontracted with 5 x 10(-8) M carbachol (an approximate median effective concentration) in a concentration-dependent manner. However, atriopeptin I failed to induce significant relaxation of the muscle. Similar results were obtained when 3 x 10(-6) M histamine or 5 x 10(-7) M serotonin was used as the contracting agent. However, the relaxant effects of ANF, atriopeptin II, and atriopeptin III were much less when a higher concentration of carbachol or 30 mM K+ was used as the contractile agent. Maximally inhibitory concentration (IC50) values of ANF, atriopeptin II, and atriopeptin III for inhibition of muscle contraction induced by 5 x 10(-8) M carbachol ranged from 3.8 to 8.3 x 10(-9) M, indicating that these peptides have intermediate potency between isoproterenol (IC50, 2.0 x 10(-9) M) and sodium nitroprusside (IC50, 2.0 x 10(-8) M). Treatment of the muscle with 3 x 10(-7) M ANF slowed the rate of tension development of the muscle by 10(-7) M carbachol. Tissue levels of cAMP were not influenced by any of the atrial peptides at concentrations of 10(-9)-10(-6) M; however, cGMP levels were increased about five- to ninefold.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishii
K
K
Department of Medicine, Stanford University School of Medicine, Palo Alto, California 94304.
Murad
F
F
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D009599:Nitroprusside; D012701:Serotonin; D006632:Histamine; D009320:Atrial Natriuretic Factor; D002217:Carbachol; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D007545:Isoproterenol; D015056:1-Methyl-3-isobutylxanthine