Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transmural nerve stimulation (TNS) of the right atria in vitro produced positive and negative chronotropic responses in rats and guinea pigs. The negative component appeared only temporarily soon after the cessation of TNS and was usually masked by the positive component. The positive and negative chronotropic responses were accompanied by an increase and decrease in contractile force, respectively. Atenolol (3 X 10(-6) M) decreased and atropine (10(-6) M) potentiated the TNS-induced positive chronotropic response. In the presence of both atenolol and atropine, TNS accelerated the heart rate markedly in the right atria of guinea pigs and slightly in those of rats. TNS-induced acceleration of the heart rate was also observed in surgically sympathectomized or reserpine-pretreated (5 mg/kg/48 hr and 2.5 mg/kg/24 hr i.p.) right atrium, in which tyramine (up to 10(-4) M) exerted no appreciable effect. Inasmuch as tetrodotoxin (10(-6) M) almost abolished the TNS-induced chronotropic response, this atenolol- and atropine-resistant response is likely mediated by nonadrenergic noncholinergic (NANC) nerve(s). The NANC nerve-mediated positive chronotropic response was not affected by diphenhydramine (10(-6) M), cimetidine (10(-6) M), methysergide (10(-6) M) and hexamethonium (3 X 10(-6) M). The NANC nerve-mediated response was relatively slow at the onset yet long-lasting compared with adrenergic and cholinergic responses, suggesting that the neurotransmitter of the NANC nerve is a certain substance which may be inactivated more slowly than biogenic amines. Histochemical studies demonstrated the presence of vasoactive intestinal polypeptide-like and substance P-like immunoreactive nerves in the right atrium, as well as catecholamine-fluorescence and acetylcholinesterase-positive nerves.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological analysis of autonomic innervation of the right atria of rats and guinea pigs: demonstration of nonadrenergic noncholinergic nerves. 242 43

The cental actions of the lipophilic cholinesterase inhibitor physostigmine were investigated by infusing very low doses (0.8 micrograms up to 18 micrograms per kg) into the left vertebral artery of the anaesthetized cat. A dose as low as 2.7 micrograms per kg reduced blood pressure by about 35%. High doses caused bradycardia. Occlusion of the right vertebral artery shifted the dose-response curve to the left. It seems likely that the hypotension was due to stimulation of muscarinic receptors in the pontomedullary region, since pretreatment with dexetimide administered via the vertebral artery strongly reduced the effect. Mecamylamine and the adrenergic blocking agents metoprolol and piperoxan, infused into the vertebral artery, could not reduce the depressor response and the bradycardic action. Both bilateral cervical vagatomy and peripherally applied N-methylatropine did not change the hypotensive action of physostigmine. This observation points towards a reduction of sympathetic outflow as the possible cause of the depressor effect. Atenolol, given intravenously, diminished the bradycardia to a great extent, whereas N-methylatropine did not significantly alter the negative chronotropic action of physostigmine. These results suggest a dominant role for the sympathetic system in reducing cardiac frequency. After intravenous administration, only doses higher than 28 micrograms per kg evoked hypotension, which could not be blocked by intravenously administered N-methylatropine. However, centrally infused dexetimide considerably antagonized this effect, indicating that the hypotension was brought about by a central action and not evoked peripherally. Application of the drug via the external carotid arteries resulted in hypotension after considerably higher doses than those following administration via the vertebral artery, indicating the pontomedullary region as the main site of action. It is concluded that the present experimental data obtained with physostigmine support the hypothesis that ACh might have a transmitter role in the central haemodynamic control.
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PMID:Central cardiovascular effects of physostigmine in the cat; possible cholinergic aspects of blood pressure regulation. 611 63