Change in muscarinic modulation of transmitter release in the rat urinary bladder after spinal cord injury.
Muscarinic facilitation of 14C-ACh release from post-ganglionic parasympathetic nerve terminals was studied in bladder strips prepared from spinal intact (SI) and spinal cord transected (SCT) rats. The spinal cord was transected at the lower thoracic spinal segments 3 weeks prior to the experiments. Using non-facilitatory stimulation (2 Hz) the release of ACh in spinal intact rats did not change in the presence of a non-specific muscarinic antagonist, atropine (100 nM), an M(1) specific antagonist (pirenzepine, 50 nM) or an M(1)-M(3) specific antagonist (4-DAMP, 5 nM). However, during a facilitatory stimulation paradigm (10 Hz or 40 Hz, 100 shocks) atropine and pirenzepine, but not 4-DAMP inhibited the release of ACh in bladders from spinal intact rats, indicating an M(1) receptor-mediated facilitation. In spinal cord transected rats, 2 Hz stimulation-induced release was significantly inhibited by atropine or 4-DAMP but not by pirenzepine indicating that a pre-junctional facilitatory mechanism mediated via M(3) muscarinic receptors could be induced by a non-facilitatory stimulation paradigm after spinal injury. In bladders of spinal cord transected rats, 10 Hz stimulation-evoked release of ACh was also inhibited by atropine and 4-DAMP (5 nM) but not by pirenzepine (50 nM). These results indicate that pre-junctional muscarinic receptors at cholinergic nerve endings in the bladder change after chronic spinal cord injury. It appears that low affinity M(1) muscarinic receptors are replaced by high affinity M(3) receptors. This change in modulation of ACh release may partly explain the bladder hyperactivity after chronic spinal cord injury.
Somogyi
George T
GT
Department of Pharmacology, University of Pittsburgh, Pittsburgh, PA 15261, USA. gsomogyi@bcm.tmc.edu
Zernova
Ganna V
GV
Yoshiyama
Mitsuharu
M
Rocha
Jeova N
JN
Smith
Christopher P
CP
de Groat
William C
WC
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000378:metabolism*; D001743:Urinary Bladder / Q000378:metabolism*; D001750:Urinary Bladder, Neurogenic / Q000378:metabolism
D018727:Muscarinic Antagonists; D018377:Neurotransmitter Agents; D010880:Piperidines; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D010890:Pirenzepine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium