Carbachol induces granular cell exocytosis and serotonin release in rabbit cerebral arteries.
Previously, we reported that rabbit cerebral arteries contain mast cells that frequently establish close contacts with parasympathetic-like nerve fibers. Here we have examined the possible function of this link by comparing the effects of carbachol and compound 48/80 on mast cell morphology and on the serotonin (5-HT) and histamine content of these arteries. In vivo, 2 micrograms/min of compound 48/80 or 1 micrograms/min of carbachol was infused for 30 min into one internal carotid artery of pentobarbital anesthetized rabbits, the contralateral artery being infused with vehicle. In vitro, the action of 10(-6) M carbachol was tested on isolated middle cerebral artery trees (MCAs) in the presence or absence of 10(-7) M atropine. The effects of carbachol were also tested in vitro on sympathectomized arteries. The 5-HT and histamine contents of all MCAs were measured by radioenzymatic assay, and fragments were prepared for electron microscopy. No histamine was detectable in any artery studied. The 5-HT content of arteries from control animals and those perfused with vehicle (in vivo) or incubated in the physiological solution (in vitro) was 250-300 pmol/mg protein. Both compound 48/80 and carbachol reduced this amount by approximately 50% and induced a marked degranulation of mast cells. Both secretion and degranulation were dramatically blocked in vitro by atropine. No difference in the 5-HT content was observed between intact and sympathectomized arteries under any condition. We conclude that a large proportion of rabbit cerebrovascular 5-HT is stored in mast cells and that cholinergic nerve activation could theoretically release this pool by acting on mast cell muscarinic receptors.
Reynier-Rebuffel
A M
AM
Laboratoire de Recherches Cérébrovasculaires, UA 641 Centre National de la Recherche Scientifique, Université Paris VII, Paris, France.
Callebert
J
J
Dimitriadou
V
V
Mathiau
P
P
Launay
J M
JM
Seylaz
J
J
Aubineau
P
P
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002343:Carotid Artery, Internal; D002536:Cerebral Arteries / Q000378:metabolism*; D003470:Culture Media; D005089:Exocytosis / Q000187:drug effects*; D006098:Granulocytes / Q000187:drug effects* / Q000648:ultrastructure; D007269:Injections, Intra-Arterial; D008297:Male; D011817:Rabbits; D012701:Serotonin / Q000378:metabolism*; D013562:Sympathectomy; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D003470:Culture Media; D012701:Serotonin; D003189:p-Methoxy-N-methylphenethylamine; D002217:Carbachol