Release of endogenous acetylcholine from a vascularly perfused rat stomach in vitro; inhibition by M3 muscarinic autoreceptors and alpha-2 adrenoceptors.
We measured endogenous overflow of acetylcholine (ACh) from a vascularly perfused rat stomach in vitro with modified Krebs-Ringer solution containing 100 microM physostigmine. Evoked ACh overflow by vagal stimulation at 2.5 Hz for 2 min was abolished by tetrodotoxin (3 x 10(-7) M) or Ca++ removal and reduced by hexamethonium (10(-4) M). The evoked overflow was inhibited by oxotremorine (10(-7) to 10(-5) M), but not attenuated by 4-(N-[3-chlorophenyl]carbamoyloxy)-2-butynyltrimethylammonium chloride (10(-6) and 10(-5) M). The evoked ACh overflow was enhanced by atropine (10(-9) to 10(-6) M), 4-diphenylacetoxy-N-methylpiperidine (10(-8) to 10(-6) M), methoctramine (10(-8) to 10(-6) M) and pirenzepine (10(-8) to 10(-6) M) in a concentration-dependent manner with the following potency; atropine > 4-diphenylacetoxy-N-methylpiperidine > methoctramine > pirenzepine. In the presence of 10(-6) M atropine, clonidine (10(-8) and 10(-7) M), but not phenylephrine (10(-7) and 10(-6) M), concentration-dependently decreased the evoked overflow of ACh at 1 Hz. Electrical stimulation of periarterial gastric sympathetic nerves (5 and 10 Hz for 2 min) frequency-dependently inhibited the evoked ACh overflow at 1 Hz in the presence of atropine and sympathetic inhibition mediated at 5 Hz was abolished by 10(-6) M rauwolscine, but not by 10(-6) M prazosin. These results indicate that the ACh release from gastric parasympathetic neurons is inhibited by M3 muscarinic autoreceptors and alpha-2 adrenoceptors.
Yokotani
K
K
Department of Pharmacology, Kochi Medical School, Nankoku, Japan.
Okuma
Y
Y
Nakamura
K
K
Osumi
Y
Y
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency; D003000:Clonidine / Q000494:pharmacology; D003959:Diamines / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D005753:Gastric Mucosa / Q000098:blood supply / Q000294:innervation / Q000378:metabolism*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists; D010095:Oxotremorine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D010656:Phenylephrine / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D013270:Stomach / Q000098:blood supply / Q000294:innervation / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D003959:Diamines; D006584:Hexamethonium Compounds; D018727:Muscarinic Antagonists; D010276:Parasympatholytics; D010880:Piperidines; D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D010656:Phenylephrine; D018738:Hexamethonium; D010890:Pirenzepine; D013779:Tetrodotoxin; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D010095:Oxotremorine; D001285:Atropine; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium; D003000:Clonidine; D000109:Acetylcholine; C054938:methoctramine; D002118:Calcium