RT Journal Article
SR Electronic
T1 ADP beta S induces contraction of the human isolated urinary bladder through a purinoceptor subtype different from P2X and P2Y.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 193
OP 197
VO 269
IS 1
A1 S Palea
A1 M Corsi
A1 C Pietra
A1 W Artibani
A1 A Calpista
A1 G Gaviraghi
A1 D G Trist
YR 1994
UL http://jpet.aspetjournals.org/content/269/1/193.abstract
AB The classification of purinergic receptors is seriously hampered by the lack of specific antagonists. Furthermore, there is increasing evidence that other purinoceptor subtypes may exist that are different than the relatively well characterized P2X, P2Y, P2Z and P2T. Human isolated urinary bladder was reported to contract in response to challenge with alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP) and adenosine 5'-triphosphate (ATP), probably through activation of P2X purinoceptors. In this work, we tried to classify the purinoceptors subtypes present in human detrusor muscle by using adenosine 5'-[beta-thio]diphosphate (ADP beta S), alpha,beta-MeATP, 2-methylthio adenosine 5'-triphosphate (2-MeSATP), ATP and uridine 5'-triphosphate (UTP). We also examined the activity of two putative P2 antagonists (p-chloromercuribenzensulfonic acid [PCMBS] and Reactive Blue 2 [RB-2]). The agonist rank order of potency was alpha,beta-MeATP = ADP beta S > 2-MeSATP > ATP > UTP. Cumulative responses to alpha,beta-MeATP induced a very rapid desensitization, but responses to alpha,beta-MeATP and ADP beta S, both at 100 microM, were additive. PCMBS antagonized ADP beta S-induced contractions with a pKB of 6.49, but it was inactive against alpha,beta-MeATP. The putative P2Y antagonist RB-2 had no effect against ADP beta S-induced contraction. We conclude that human detrusor muscle contains two contractile purinoceptor subtypes. One is activated by alpha,beta-MeATP and is probably the P2X subtype; the other is activated by ADP beta S and appears to be different from those accepted by the current classification. The similarity between our results and those obtained by other investigators is discussed.