Evidence for purinergic neurotransmission in the urinary bladder of pithed rats.
The purpose of this study was to investigate the contribution of adenosine-5'-triphosphate (ATP) to segmental (L6-S2) spinal electrical stimulation evoked increases in intra-vesical pressure in pithed rats. Exogenous ATP and substance P produced dose-dependent increases in intra-vesical pressure (ED10 mmHg (dose required to elicit 10 mmHg increase in intra-vesical pressure)= 1.7 mg/kg and 1.1 microg/kg, i.v., respectively). Desensitisation (or antagonism) of P2x purinoceptors with alpha,beta-methylene ATP (alpha,beta-meATP; 30 microg/kg per min, i.v.) or pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 10 mg/kg, i.v.) significantly (p < 0.05) antagonized the intra-vesical pressure responses to ATP (> 8 and 3.6-fold increase in ED10 mmHg, respectively) but had no significant effect on intra-vesical pressure responses to substance P. Spinal stimulation evoked frequency-dependent increases in intra-vesical pressure (EF20 mmHg (frequency required to produce 20 mmHg increase in intra-vesical pressure) = 3.4 Hz). Blockade of muscarinic cholinoceptors and adrenoceptors with atropine (3 mg/kg, i.v.), propranolol (3 mg/kg, i.v.) and phentolamine (10 mg/kg, i.v.) produced marginal attenuation of the intra-vesical pressure responses to spinal stimulation indicating a major non-adrenergic non-cholinergic (NANC) component in the overall response. The NANC responses were significantly (p < 0.05) antagonized by alpha,beta-meATP (30 microg/kg per min, i.v.) and PPADS (10 mg/kg, i.v.) (> 2.6-fold increase in EF20 mmHg), consistent with involvement of a purinergic neurotransmitter, presumably ATP. Comparative studies in young (4-6 months) and old (21-23 months) Fischer rats revealed no age-dependent changes in the relative contribution of the cholinergic and purinergic systems, with the latter being the dominant one. These findings suggest that purinergic neurotransmission, presumably mediated by ATP acting via P2x purinoceptors, represents a major component of excitatory innervation to the urinary bladder in pithed rats.
Hegde
S S
SS
Center for Biological Research, Roche Bioscience, Palo Alto, CA 94304, USA. sharath.hegde@roche.com
Mandel
D A
DA
Wilford
M R
MR
Briaud
S
S
Ford
A P
AP
Eglen
R M
RM
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D004558:Electric Stimulation; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D011312:Pressure; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000502:physiology*; D013127:Spinal Nerves / Q000502:physiology; D013373:Substance P / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation / Q000502:physiology*
D018674:Adrenergic Antagonists; D005730:Ganglionic Blockers; D018727:Muscarinic Antagonists; D058919:Purinergic P2 Receptor Antagonists; D011983:Receptors, Purinergic; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D013373:Substance P; D011732:Pyridoxal Phosphate; D001285:Atropine; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate