Mc. Olianas et P. Onali, IMPAIRMENT OF MUSCARINIC STIMULATION OF ADENYLYL-CYCLASE BY HEPARIN IN RAT OLFACTORY-BULB, Life sciences, 61(5), 1997, pp. 515-522
Citations number
25
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
In rat olfactory bulb membranes, the stimulation of adenylyl cyclase b
y the cholinergic agonist carbachol (CCh) was markedly inhibited by he
parin at concentrations (0.3-10 mu M) that had smaller or no effects o
n the enzyme stimulations elicited by vasoactive intestinal peptide, p
ituitary adenylate cyclase activating polypeptide (PACAP), 1-isoproter
enol and corticotropin releasing hormone. Heparin did not significantl
y affect the binding of [H-3]N-methylscopolamine ([H-3]NMS) to muscari
nic receptors, but decreased the potency of CCh in displacing the boun
d radioligand in a manner similar to that of the GTP analogue guanosin
e-5'-O-(3'-thio)triphosphate (GTP gamma S). Heparin inhibited the bind
ing of [S-35] GTP gamma S to membrane G proteins stimulated by CCh mor
e potently than that elicited by PACAP. Moreover, at the same concentr
ations, heparin inhibited the muscarinic inhibition of adenylyl cyclas
e in rat striatal membranes. These data indicate that heparin impairs
the muscarinic stimulation of olfactory bulb adenylyl cyclase likely b
y interfering with the receptor-induced activation of G proteins. The
higher sensitivity to heparin of this response as compared to those di
splayed by Os-mediated enzyme stimulations provides further evidence t
hat Gi/Go, rather than Gs, mediate the muscarinic stimulation of adeny
lyl cyclase in rat olfactory bulb.