D. Gebremedhin et al., Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhibit L-type Ca2+ channel current, AM J P-HEAR, 45(6), 1999, pp. H2085-H2093
Citations number
45
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Cannabinoid CB1 receptor of cat cerebral arterial muscle functions to inhib
it L-type Ca2+ channel current. Am. J. Physiol. 276 (Heart Circ. Physiol. 4
5): H2085-H2093, 1999.-The CB1 subtype of the cannabinoid receptor is prese
nt on neurons in the brain and mediates the perceptual effects of hs-tetrah
ydrocannabinol and other cannabinoids. We found that cat cerebral arterial
smooth muscle cells (VSMC) contain the protein for the CB1 receptor and exp
ress a cDNA that has >98% amino acid homology to the CB1 cDNA expressed in
rat and human neurons. Activation of the CB1 cannabinoid receptor has been
shown to decrease the opening of N-type voltage-gated Ca2+ channels in neur
ons through a pertussis toxin-sensitive GTP-binding protein. In the present
study we tested the hypothesis that activation of the cannabinoid CB1 rece
ptor in cerebral VSMC inhibits voltage-gated Ca2+ channels and results in c
erebral vasodilation. The predominant Ca2+ current identified in cat cerebr
al VSMC is a voltage-gated, dihydropyridine-sensitive, L-type Ca2+ current.
The cannabimimetic drug WIN-55,212-2 (10-100 nM) induced concentration-dep
endent inhibition of peak L-type Ca2+ current, which reached a maximum of 8
2 +/- 4% at 100 nM (n = 14). This effect was mimicked by the putative endog
enous CB1-receptor agonist anandamide, which produced a concentration-relat
ed reduction of peak L-type Ca2+ current with a maximum inhibition (at 300
nM) of 39 +/- 4% (n = 12). The inhibitory effects of both ligands on peak L
-type Ca2+ currents were abolished by pertussis toxin pretreatment and appl
ication of the CB1-receptor antagonist SR-141716A (100 nM, n = 5), Both WIN
-55,212-2 and anandamide produced concentration-dependent relaxation of pre
constricted cerebral arterial segments that was abolished by SR-141716A. Th
ese results indicate that the CB1 receptor is expressed in cat cerebral VSM
C and that the cerebral vasculature is one of the targets for endogenous ca
nnabinoids. These findings suggest that the CB1 receptor and its endogenous
ligand may play a fundamental role in the regulation of cerebral arterial
tone and reactivity by modulating the influx of Ca2+ through L-type Ca2+ ch
annels.