Somatostatin inhibition of adenylate cyclase activity in different brain areas.
Somatostatin receptors have been identified in different brain areas but the characterization of their postreceptor effect is still lacking. In this study we analyze the somatostatin effect on adenylate cyclase activity in different brain regions, namely frontal cortex, striatum, hypothalamus and hippocampus. Somatostatin inhibited basal adenylate cyclase activity in all brain areas, being maximally effective in the frontal cortex (-42%). Moreover, somatostatin inhibited both dopamine- and norepinephrine-stimulated adenylate cyclase activity in the examined cerebral regions showing a higher effectiveness than in basal conditions. VIP stimulation of adenylate cyclase was also reduced by somatostatin. The peptide inhibited by 50% forskolin-stimulated (10 nM to 10 microM) enzyme activity in frontal cortex and hypothalamus (in hippocampus the inhibition reached only -25%) showing a non-competitive pattern of inhibition. Finally, pertussis toxin pretreatment abolished the somatostatin inhibition of forskolin-stimulated frontal cortex adenylate cyclase activity. These results show that brain somatostatin receptors are coupled in an inhibitory way with adenylate cyclase enzyme that may represent one of the postreceptor mechanisms mediating the somatostatin modulation of brain functions.
Schettini
G
G
Department of Pharmacology, II School of Medicine, University of Naples, Italy.
Florio
T
T
Meucci
O
O
Landolfi
E
E
Grimaldi
M
M
Ventra
C
C
Marino
A
A
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D005576:Colforsin; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D009638:Norepinephrine