Brain nicotinic acetyicholine receptors (nACh-Rs) blood flow (CBF) in anesthetized modulate cortical cerebral rats

• Published in: Japanese Journal of Pharmacology Vol. 76; no. suppl.1; p. 225
• Main Authors: Yoshihiro Tani, Hiroshi Uramoto, Kyoshi Saito, Masahiro Imoto, Tomochika Ohno
• Format: Journal Article
• Language: Japanese
• Published: The Japanese Pharmacological Society 1998
• ISSN: 0021-5198; 1347-3506

Previous studies have indicated that (-)-nicotine markedly increases cortical cerebral blood flow (CBF) via central nACh-Rs, independent of systemic nACh-Rs. In the present, to examine the role of nACh-Rs in modulation of cortical CBF, the inhibitory effects of several types of nACh-R antagonist on (-)-nicotine-induced changes were studied. Cortical CBF measured by laser-Doppler flowmetry and blood pressure (BP) and heart rate (HR) were continuously monitored in urethane anesthetized rats. Subcutaneous administration of (-)-nicotine and (S)-3-methyl-5-(l-methyl-2-pyrrolidiny)isoxazole (ABT-418), which reported to show high affinity for the α4β2 nACh-R subunits, increased CBF in a dosedependent manner and maximal response were observed by 1.0 and 3.0 mg/kg, respectively. On the other hand, 3-(2,4dimethoxy-benzlidene)-anabaseine (GTS-21), high affinity for α7 nACh-R subunit, was without effect. (-)-Nicotineinduced increases in CBF was blocked dose-dependently by pretreatment with dihydro-β-erythroidine (DHJβE), the competitive nACh-R antagonist that reported to be more sensitive to α4β2 subunits. In contrast, the selective nACh-R antagonist for α7 subunit, methyllycaconitine (MLA) and the partial agonist for α3 subunit, (-)-lobeline, did not affect (-)nicotine-induced increase of CBF. These results taken together indicate that (-)-nicotine induced increase of CBF may be attributed to stimulation of α4β2 subunits of nACh-Rs in the brain.