Arteriolar relaxation caused by the application of muscarinic agonists is mediated by multiple factors. One factor causes dilation only at the point of drug microapplication (local response), and a second factor causes responses remote (500 μm away) from the site of application (conducted response). This study was performed to determine if different muscarinic subtypes mediate the two responses. Arterioles of anesthetized hamster cheek pouch were studied with videomicroscopy. Muscarinic antagonists methscopolamine, scopolamine, pirenzepine, 4-DAMP (4-diphenylacetoxy-N- methylpiperidine methiodide), and AFDX-116 [(11-2[[2-[(diethylamino)methyl]- 1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido [2,3-b][1,4]benzodiazepin-6- one)] were cumulatively applied, and the K(B) for each antagonist was determined for the local and conducted responses caused by methacholine microapplication (10-4 M, 5 s). The pK(B) (local, conducted) were not significantly different for the two responses when using scopolamine (10.5, 10.4). When the antagonist AFDX-116 (5.6, 6.3), selective for muscarinic receptor (m2) subtype was applied, the K(b) was greater for the conducted response. The pK(B) was greater, however, for the local response when the ml subtype-selective pirenzepine (7.7, 6.9) or m3 subtype-selective 4-DAMP (10.1, 9.8) was applied. Thus the antagonist pK(B) ratio for on the local and conducted responses depends on the subtype selectivity of the antagonist. These data strongly suggest that different receptors are involved in the two responses.
- Cheek pouch
- Conducted responses
- Muscarinic receptors
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine