Nucleotide-evoked relaxation of rat vas deferens--a possible role for endogenous ATP released upon alpha(1)-adrenoceptor stimulation.
The possibility was tested that endogenous ATP released upon alpha(1)-adrenoceptor activation causes relaxation of the rat vas deferens smooth muscle. ATP, 2-methylthio ATP and adenosine relaxed the vas deferens precontracted with 80 mM K(+). The metabolically stable P2 receptor agonists alpha,beta-methylene ATP (alpha,beta-MeATP) and adenosine 5'-O-(2-thiodiphosphate) (ADPbetaS) had little or no effect. The adenosine P1 receptor antagonist 8-(para-sulfophenyl)theophylline did not significantly affect the response to ATP. The P2 receptor antagonist reactive blue 2 markedly reduced the relaxation (by up to 73%); suramin, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and acid blue 129 caused no change. ATP, but not alpha,beta-MeATP, also attenuated contractions elicited by noradrenaline at resting tension; reactive blue 2 blocked the inhibitory effect of ATP. Reactive blue 2, by itself, enhanced the response to noradrenaline (by up to 36%); suramin, PPADS and acid blue 129 caused no change. In the presence of the ATP-degrading enzymes apyrase and nucleotide pyrophosphatase, the facilitatory effect of reactive blue 2 was lost. Apyrase, by itself, enhanced the response to noradrenaline (by 13%). The results indicate that endogenous ATP, released from rat vas deferens smooth muscle upon alpha(1)-adrenoceptor stimulation, causes relaxation. The site of action of ATP is not a typical smooth muscle P2Y receptor.
Bültmann
R
R
Pharmakologisches Institut, Hermann-Herder-Strasse 5, D-79104 Freiburg i.Br., Germany. bueltman@pironet.de
Starke
K
K
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001081:Apyrase / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D009711:Nucleotides / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D058915:Purinergic P1 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D011755:Pyrophosphatases / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology; D013498:Suramin / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D009711:Nucleotides; D058915:Purinergic P1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1; D013873:Thionucleotides; D014227:Triazines; D014662:Vasoconstrictor Agents; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; C030812:adenosine 5'-O-(2-thiodiphosphate); C012842:Cibacron Blue F 3GA; D011732:Pyridoxal Phosphate; D013498:Suramin; D000244:Adenosine Diphosphate; C031433:8-(4-sulfophenyl)theophylline; D000255:Adenosine Triphosphate; D013806:Theophylline; D011755:Pyrophosphatases; D001081:Apyrase; C021899:nucleotide pyrophosphatase; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D011188:Potassium; D009638:Norepinephrine