Modulation of cerebral microvascular permeability by endothelial nicotinic acetylcholine receptors.
Nicotine increases the permeability of the blood-brain barrier in vivo. This implies a possible role for nicotinic acetylcholine receptors in the regulation of cerebral microvascular permeability. Expression of nicotinic acetylcholine receptor subunits in cerebral microvessels was investigated with immunofluorescence microscopy. Positive immunoreactivity was found for receptor subunits alpha3, alpha5, alpha7, and beta2, but not subunits alpha4, beta3, or beta4. Blood-brain barrier permeability was assessed via in situ brain perfusion with [14C]sucrose. Nicotine increased the rate of sucrose entry into the brain from 0.3 +/- 0.1 to 1.1 +/- 0.2 microl.g(-1).min(-1), as previously described. This nicotine-induced increase in blood-brain barrier permeability was significantly attenuated by both the blood-brain barrier-permeant nicotinic antagonist mecamylamine and the blood-brain barrier-impermeant nicotinic antagonist hexamethonium to 0.5 +/- 0.2 and 0.3 +/- 0.2 microl.g(-1).min(-1), respectively. These data suggest that nicotinic acetylcholine receptors expressed on the cerebral microvascular endothelium mediate nicotine-induced changes in blood-brain barrier permeability.
Hawkins
Brian T
BT
Program in Neuroscience, Univ. of Arizona College of Medicine, 1501 N. Campbell Ave., Tucson, AZ 85724-5050, USA.
Egleton
Richard D
RD
Davis
Thomas P
TP
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002199:Capillary Permeability; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D018738:Hexamethonium / Q000494:pharmacology; D008464:Mecamylamine / Q000494:pharmacology; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D009538:Nicotine / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*
D018733:Nicotinic Antagonists; D020033:Protein Isoforms; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D008464:Mecamylamine; D009538:Nicotine