RGD Reference Report - Differentiation of muscarinic receptors mediating negative chronotropic and vasoconstrictor responses to acetylcholine in isolated rat hearts. - Rat Genome Database

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Differentiation of muscarinic receptors mediating negative chronotropic and vasoconstrictor responses to acetylcholine in isolated rat hearts.

Authors: Hoover, DB  Neely, DA 
Citation: Hoover DB and Neely DA, J Pharmacol Exp Ther. 1997 Sep;282(3):1337-44.
RGD ID: 2303391
Pubmed: PMID:9316844   (View Abstract at PubMed)

The primary goal of this study was to determine the extent that selective muscarinic receptor antagonists could discriminate between the chronotropic and coronary vasoconstrictor responses to acetylcholine in isolated rat hearts perfused at constant flow rate. Bolus injections of acetylcholine caused dose-dependent decreases in heart rate and increases in perfusion pressure. The ED50 (95% confidence) of acetylcholine for decreasing rate was 0.463 (0.336-0.640) nmol and the dose that increased perfusion pressure by 30 mm Hg (ED30 mmHg) was 3.19 (2.00-5.08) nmol. The M2 selective antagonist methoctramine (3.16 microM) produced a 307-fold increase in the ED50 for bradycardia but had no significant effect on the pressor response to acetylcholine. In marked contrast, the M3 antagonist hexahydrosiladifenidol displayed a distinct preference for inhibiting coronary vasoconstrictor responses to acetylcholine. When present at 316 nM, this drug produced a 66-fold increase in the ED30 mmHg but only a 6-fold increase in the ED50 for bradycardia. The M1 selective antagonist pirenzepine (316 nM) produced a 5- to 7-fold increase in both parameters. Pretreatment with pertussis toxin (25 microg/kg, i.p.) essentially eliminated acetylcholine-evoked bradycardia although pressor responses persisted with some reduction. These observations demonstrate that cardiac and coronary vascular effects of acetylcholine can be clearly discriminated with specific muscarinic antagonists. Furthermore, they provide evidence that the M3 receptor subtype mediates the vasoconstrictor effect of acetylcholine on resistance vessels in rat heart.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Chrm3Ratnegative regulation of heart rate by acetylcholine  IMP  RGD 
Chrm3Ratpositive regulation of vasoconstriction  IMP  RGD 
Chrm3Ratresponse to acetylcholine  IMP hexahydrosiladifenidolRGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Chrm3RatG protein-coupled acetylcholine receptor binding  IDA hexahydrosiladifenidolRGD 

Objects Annotated

Genes (Rattus norvegicus)
Chrm3  (cholinergic receptor, muscarinic 3)


Additional Information