Journal of Neuroscience, Vol 3, 2487-2493, Copyright © 1983 by Society for Neuroscience
Activators of cyclic adenosine 3':5'-monophosphate accumulation in rat hippocampal slices: action of vasoactive intestinal peptide (VIP)
AM Etgen and ET Browning
The present experiments tested the ability of putative neurotransmitters
and neuromodulators to regulate cyclic adenosine 3':5'-monophosphate (cAMP)
levels in rat hippocampal slices. Slices from ovariectomized adult female
rats were equilibrated for 1 hr and incubated for 20 min with various test
compounds, and cAMP was extracted and quantified using a competitive
protein-binding assay. Norepinephrine, adenosine, histamine, and
prostaglandins E1 and E2 alpha, induced moderate (1.5- to 5-fold) increases
in cellular cAMP, whereas dopamine, serotonin, prostaglandin F2 alpha, and
glutamate were relatively ineffective. Most striking was the observation
that vasoactive intestinal peptide (VIP) produced marked elevation
(approximately 80-fold at 6 microM) of hippocampal slice cAMP content. In
contrast, other peptides produced only 2-fold increased (glucagon,
somatostatin) or no change in cellular cAMP levels (enkephalins, LHRH, ACTH
analogue, arginine vasopressin). Significant elevations in cAMP were seen
with VIP concentrations as low as 20 nM; the cAMP response was half-maximal
at 1 microM VIP and maximized between 10 and 20 microM. At maximally
effective concentrations, VIP was 86% as effective in increasing cAMP as
maximal concentrations of forskolin, a compound which activates adenylate
cyclase in most cell types. The cAMP response to 10 microM VIP was
pronounced after a 1-min incubation (16-fold elevations) and was maximal at
30 min (140-fold elevation). When slices from other brain areas were
compared, it was found that regions known to contain high levels of VIP
(cerebral cortex) also responded to VIP treatment with 30- to 50-fold
elevations in cAMP.(ABSTRACT TRUNCATED AT 400 WORDS)