The signalling pathway which causes contraction via P2-purinoceptors in rat urinary bladder smooth muscle.
1. The signalling pathway which causes contractions to adenosine 5'-O-2-thiodiphosphate (ADPbetaS) and alpha,beta-methylene adenosine 5'-diphosphate (alpha,beta-Me ADP) was investigated in rat urinary bladder smooth muscle by measuring isotonic tension. 2. The responses to 10 microM alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-Me ATP) in 0 and 3.6 mM Ca2+ were 5.9+/-1.3 (n=10) and 122.2+/-6.4 (n=8) % respectively of those obtained in 1.8 mM Ca2+, whereas those to 100 microM ADPbetaS were 34.6+/-3.3 (n=8) and 96.8+/-7.2 (n = 8) %, in 0 and 3.6 mM Ca2+, respectively. In both experimental conditions, the responses to the two agonists expressed as % of the control responses were significantly different (P<0.01). 3. Indomethacin at high concentrations (>1 microM) decreased the responses to alpha,beta-Me ATP (10 microM), ADPbetaS (100 microM) and alpha,beta-Me ADP (100 microM). However, no significant difference was obtained between the responses to all the agonists at 30 microM indomethacin. 4. 2-Nitro-4-carboxphenyl n,n-diphenylcarbamate (NCDC) at concentrations between 1 microM and 100 microM concentration-dependently decreased the responses to ADPbetaS (100 microM) and alpha,beta-Me ADP (100 microM) and almost completely inhibited them at 100 microM. Although the responses to alpha,beta-Me ATP (10 microM) were also inhibited by the drug, at 50 and 100 microM NCDC the responses to alpha,beta-Me ATP were significantly larger than those to ADPbetaS and alpha,beta-Me ADP (P<0.01). 5.NCDC 100 microM significantly inhibited the KCl-induced contraction to 65.9+/-4.9% (n=6) of the control (P<0.01). 6. It is suggested that the contraction via ADPbetaS-sensitive receptors in the rat urinary bladder smooth muscle mainly depends on Ca2+ ions liberated from intracellular Ca2+ stores, though the contribution of Ca2+ ions from the extracellular space cannot be neglected. The release of Ca2+ ions from stores is mainly mediated by the production of inositol trisphosphate (IP3) via the activation of phospholipase C.
Naramatsu
M
M
Department of Physiology, Nihon University School of Medicine, Tokyo, Japan.
Yamashita
T
T
Kokubun
S
S
D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D048448:Phenylcarbamates; D011189:Potassium Chloride / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
D002219:Carbamates; D004963:Estrenes; D048448:Phenylcarbamates; D011760:Pyrrolidinones; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; C523965:alpha,beta-methyleneadenosine 5'-diphosphate; C025508:2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C030812:adenosine 5'-O-(2-thiodiphosphate); D000244:Adenosine Diphosphate; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D007213:Indomethacin