Cholecystokinin induces cerebral vasodilatation via presynaptic CCK2 receptors: new implications for the pathophysiology of panic.
The authors report that cholecystokinin (CCK), via its subtype 2 receptor (CCK2R) located presynaptically on cerebral arteries, mediates the release of nitric oxide (NO), which induces vasodilatation. Whereas CCK octapeptide and its fragment CCK tetrapeptide (CCK-4) lack a direct effect on the smooth muscle of pial vessels, the authors showed that both CCK peptides modulate the neurogenic responses in bovine cerebral arteries. The neurogenic vasodilatation induced by CCK-4 was blocked by the CCK2R antagonist, L-365,260, and antagonized by neuronal NO synthase (nNOS) inhibitors, but was independent of the endothelium. In whole-mount arteries, CCK2Rs were detected in nerve fibers and colocalized with nNOS and synaptophysin. The findings provide, for the first time, a neural mechanism by which CCK may increase cerebral blood flow.
Sánchez-Fernández
Cristina
C
Departamento de Farmacologia, Universidad Complutense, Madrid, Spain.
González
Carmen
C
Mercer
Linda D
LD
Beart
Philip M
PM
Ruiz-Gayo
Mariano
M
Fernández-Alfonso
María S
MS
D000818:Animals; D002417:Cattle; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology*; D066298:In Vitro Techniques; D019001:Nitric Oxide Synthase / Q000502:physiology; D052248:Nitric Oxide Synthase Type I; D016584:Panic Disorder / Q000503:physiopathology; D010841:Pia Mater / Q000098:blood supply; D017729:Presynaptic Terminals / Q000378:metabolism*; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology; D013758:Tetragastrin / Q000494:pharmacology; D014018:Tissue Distribution; D014664:Vasodilation
D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D002766:Cholecystokinin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D012844:Sincalide