Contractile activity of ATP and diadenosine tetraphosphate on urinary bladder in the rat: role of A1- and P2X-purinoceptors and nitric oxide.
1. Both adenosine-5'-triphosphate (ATP) and diadenosine tetraphosphate (AP4A) produced a dose-dependent contraction of the isolated rat urinary bladder rings. AP(4)A dose-response curve was to the left of that of ATP, and maximum response was greater than that produced by ATP. 2. 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), the A1-purinergic receptor blocker (0.01 mm) significantly inhibited the ATP- and AP4A-induced contractions at the whole dose range. The inhibition was between 31-41%, and 15-25% for ATP and AP4A respectively. 3. Pyridoxal phosphate 6-azophenyl-2',4'-disulphonic acid (PPADS), the P2X-purinoceptor antagonist (0.01 mm) potently inhibited the bladder contractions in response to ATP and AP4A by around 75-80%. 4. The nitric oxide (NO) precursor L-arginine reduced the bladder contractile response to ATP by about 22-41% and that of AP4A to a lesser extent by around 20-32%. 5. The nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), did not produce any significant effect on ATP except for a weak inhibition of about 14% at the lowest dose of ATP. The contractions in response to AP4A were only slightly reduced by L-NAME by about 20%. 6. In conclusion, the contractile response of the bladder to ATP and to the dinucleotide AP4A is mediated mainly through P2X-purinoceptors and A1-purinergic receptors. In the detrusor muscle, NO donation possesses an inhibitory effect on ATP-mediated contractility more than that produced by the dinucleotide AP4A.
Khattab
M M
MM
Department of Pharmacology, College of Pharmacy, King Saud University, PO Box 2457, Riyadh 11451, Saudi Arabia.
Al-Hrasen
M N
MN
El-Hadiyah
T M
TM
D058916:Adenosine A1 Receptor Antagonists; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D001743:Urinary Bladder / Q000187:drug effects* / Q000201:enzymology; D014970:Xanthines / Q000494:pharmacology
D058916:Adenosine A1 Receptor Antagonists; D015226:Dinucleoside Phosphates; D058919:Purinergic P2 Receptor Antagonists; D043682:Receptor, Adenosine A1; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D014970:Xanthines; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D009569:Nitric Oxide; C020733:diadenosine tetraphosphate; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester