M1 muscarinic receptor-mediated facilitation of acetylcholine release in the rat urinary bladder.
1. Release of [3H]ACh in response to electrical field stimulation (10 Hz) was measured in strips of rat urinary bladder and cardiac atrial tissues previously incubated with [3H]choline. 2. The volley output of [3H]ACh release was positively correlated with frequency of stimulation in the urinary bladder but negatively correlated in the atrium. 3. The quantity of [3H]ACh release was influenced by the pattern and duration of stimulation. Continuous stimulation (CS) with trains of 100 shocks released 10 times larger amounts of ACh than the same number of shocks presented as short trains of intermittent stimulation (IS): ten shocks per train with 5 s inter-train intervals. 4. The facilitation of transmitter release was antagonized completely by the administration of atropine (1 microM) or pirenzepine (0.05 microM), a selective M1 antagonist. Eserine, an anticholinesterase agent, markedly facilitated ACh release induced by CS and IS. This effect was blocked by atropine. 5. Release of ACh from atrial strips did not exhibit CS-induced facilitation. Eserine decreased IS- and CS-evoked ACh release in the atrium. 6. It is concluded that continuous stimulation of postganglionic cholinergic nerves in the rat urinary bladder leads to the activation of M1 muscarinic, facilitatory presynaptic receptors which enhance the release of ACh. Presynaptic facilitation may be an important mechanism for modulating neural input to the bladder during micturition.
Somogyi
G T
GT
Department of Pharmacology, University of Pittsburgh, PA 15261.
Tanowitz
M
M
de Groat
W C
WC
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D016275:Atrial Function; D002118:Calcium / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000502:physiology; D001743:Urinary Bladder / Q000294:innervation / Q000378:metabolism* / Q000502:physiology
D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D017661:Receptors, Presynaptic; D010830:Physostigmine; D002794:Choline; D000109:Acetylcholine; D002211:Capsaicin; D002118:Calcium