Muscarinic receptor subtype (M1) identification on rabbit pulmonary vascular endothelium in vivo.
We have investigated the presence of M1-subtype muscarinic receptors on pulmonary vascular endothelium in vivo. Utilizing multiple indicator-dilution techniques, we studied [3H]-pirenzepine ([3H]-PNZ; a selective M1 receptor antagonist) binding during a single transpulmonary pass in anesthetized, artificially ventilated rabbits, before and after administration of 4.3 mumol/kg of the nonselective muscarinic receptor antagonist atropine. [14C]-Dextran (MW = 70,000-90,000) served as the intravascular indicator. Before atropine administration, approximately 20% of [3H]-PNZ was lost (i.e., presumed bound to PNZ-specific and nonspecific sites) during a single pass through the pulmonary microvasculature. A significant decrease in [3H]-PNZ binding occurred 90 min after atropine (to approximately 60% of total initial binding), but not after saline, reflecting the loss of specific binding to M1 receptors. These data are in support of previous findings from our laboratory indicating a pressor response to M1 receptor stimulation in the rabbit pulmonary circulation as well as an endothelium-dependent contractile response to M1 receptor stimulation in vitro.
Orphanos
S E
SE
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta.
Catravas
J D
JD
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005070:Evans Blue; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D011976:Receptors, Muscarinic; D010890:Pirenzepine; D005070:Evans Blue; D001285:Atropine