Rat urinary bladder-derived relaxant factor: Studies on its nature and release by coaxial bioassay system

• Published in: European journal of pharmacology Vol. 591; no. 1; pp. 273 - 279
• Main Authors: Bozkurt, Turgut Emrah, Sahin-Erdemli, Inci
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 04-09-2008; Elsevier
• Subjects: Acetylcholine - administration & dosage; Acetylcholine - pharmacology; Adenylyl Cyclases - metabolism; Animals; Anococcygeus muscle; Biological and medical sciences; Biological Assay - methods; Bladder-derived relaxant factor; Coaxial bioassay; Cyclic AMP-Dependent Protein Kinases - metabolism; Dose-Response Relationship, Drug; Male; Medical sciences; Muscle Relaxation - drug effects; Muscle Relaxation - physiology; Neurons - metabolism; Pharmacology. Drug treatments; Rat; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2 - metabolism; Urinary bladder; Urinary Bladder - drug effects; Urinary Bladder - metabolism; Coaxial bioassay; Bladder-derived relaxant factor; Urinary bladder; Rat; Anococcygeus muscle; Vertebrata; Mammalia; Urinary system; Animal; Rodentia; Urinary bladder,Coaxial bioassay,Bladder-derived relaxant factor,Anococcygeus muscle,(Rat); Muscle; Release
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.06.083

The present study was designed to characterize the urinary bladder-derived relaxant factor that was demonstrated by acetylcholine-induced relaxation response in a coaxial bioassay system consisting of rat bladder as the donor organ and rat anococcygeus muscle as the assay tissue. The concentration-dependent relaxation to acetylcholine (10 nM–1 mM) was inhibited by atropine but was not altered by the antagonists of calcitonin gene-related peptide (CGRP 8–37), vasoactive intestinal peptide (VIP 6–28), tachykinin NK1 (L-732138), tachykinin NK2 (MEN-10376), tachykinin NK3 (SB-218795), purinergic P2 (PPADS) and adenosine (CGS 15943) receptors as well as alpha-chymotrypsin. Adenylate cyclase inhibitor SQ-22536 and protein kinase A inhibitor KT-5720 significantly inhibited the acetylcholine response while guanylate cyclase inhibitor ODQ, and protein kinase C inhibitor H-7 did not have any effect. The P2X agonist α,β-methylene ATP (10 nM–0.1 mM) also produced concentration-dependent relaxation response that was inhibited by PPADS, SQ-22536 and KT-5720 in the coaxial bioassay system. In bladder strips, acetylcholine and α,β-methylene ATP elicited concentration-dependent contractions that were not altered in the presence of SQ-22536 and KT-5720. In conclusion, the urinary bladder-derived relaxant factor that was recognized by the coaxial bioassay system is neither a peptide of the bladder neurons nor a purinergic mediator but adenylate cyclase and protein kinase A are involved in its release and/or relaxant effect. Furthermore, activation of purinergic P2X receptors besides the muscarinic receptors leads to the release of this factor.