Relaxant effects of nucleotides in guinea pig isolated, perfused trachea: lack of involvement of prostanoids, Cl- channels and adenosine.
In higher concentrations (> 3 x 10(-4) M) than those causing contractile responses. ATP relaxed the smooth muscle of the guinea pig perfused trachea. Here we examined the relaxant effects of nucleotides. ATP and its nonhydrolyzable congener, beta, gamma-methylene ATP (APPCP), were approximately 4- and approximately 117-fold, respectively, more potent when applied separately to the serosal (extraluminal, EL) surface compared to the mucosal (intraluminal, IL) surface of methacholine (3 x 10(-7) M; EL)-contracted tracheae. APPCP was orders of magnitude more potent than ATP in both EL and IL compartments. EL UTP did not cause relaxation; IL UTP was nearly devoid of activity. The order of EL and IL activity (APPCP >> ATP) was unusual for nucleotide-induced relaxation of smooth muscle. Relaxation to ATP was not inhibited by the Cl- channel blocker 4,4'-diisothiocyano-2,2'-stilbene disulfonate (10(-4) M) or by the cyclo-oxygenase inhibitor indomethacin (3 x 10(-6) M), in contrast to the inhibitory effects of these drugs on contraction to ATP. The adenosine receptor antagonist 8-phenyltheophylline (10(-6) M) had no effect on relaxation to ATP or APPCP. Our findings indicate that Cl- channels, prostaglandins and adenosine are not involved in relaxation to adenine nucleotides.
Physiology Section, National Institute for Occupational Safety and Health, Morgantown, West Virginia.
J S
JS
Fedan
J J
JJ
Belt
L X
LX
Yuan
D G
DG
Frazer
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D018118:Chloride Channels; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000502:physiology*; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009711:Nucleotides / Q000494:pharmacology*; D011453:Prostaglandins / Q000494:pharmacology*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000502:physiology; D014544:Uridine Triphosphate / Q000494:pharmacology
D018118:Chloride Channels; D008565:Membrane Proteins; D009711:Nucleotides; D011453:Prostaglandins; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D014544:Uridine Triphosphate; D007213:Indomethacin