Regulation by secretin, vasoactive intestinal peptide, and somatostatin of cyclic AMP accumulation in cultured brain cells.

Abstract

Secretin stimulates the accumulation of cyclic AMP (half maximally stimulating concentration: 10-20 nM) in cultured mouse brain cells mainly consisting of glioblasts. Vasoactive Various peptides are known to be common to the brain and the gastrointestinal tract and pancreas (1). Some of these peptides (e.g., substance P, somatostatin, enkephalin) have been shown to elicit specific behavioral changes or changes in specific neuron firing rates or patterns (for review see refs. 2-4). They are, therefore, hypothesized to act on neurons as neuromodulators or neurotransmitters. Some neurohormones are also known to act on glial cells by regulating the intracellular level of cyclic AMP (for review see ref. 5). The possibility had to be considered that this would not only hold for biogenic amines such as norepinephrine but also for peptide hormones. Therefore, we investigated the effects of peptide hormones on the accumulation of cyclic AMP in glial cell cultures derived from neonatal mouse brain. We report-here that somatostatin inhibits the basal and the hormone-induced accumulation of cyclic AMP in such primary cultures. Furthermore, we report that the gastrointestinal hormones secretin and vasoactive intestinal peptide (VIP) stimulate the accumulation of cyclic AMP in these cultures, probably via different types of receptors. Thus a possible role of peptide hormones in the function of glial cells is indicated. In addition, the results suggest that secretin or a closely related compound might exert regulatory influence in the brain. A preliminary report of some of these results has been presented at a conference (6).MATERIALS AND METHODS Materials. Dulbecco's modified Eagle's medium and fetal bovine serum (GIBCO) were from C. Roth, Karlsruhe, Federal Republic of Germany. A partially purified preparation of VIP (porcine) was kindly donated by V. Mutt, Stockholm, Sweden. Isolated somatostatin (cyclic; bovine) was from Beckman,

Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism.

“…However, a direct interaction of secretin with specific secretin receptors cannot be excluded, particularly in view of the fact that this peptide has been demonstrated to stimulate cyclic AMP formation in cultured mouse brain cells through receptors separate from those for VIP (43). Although a secretin-like bioactive material has been extracted from pig brain (44), a clear neurotransmitter function has not yet been attributed to this unidentified peptide.…”

Substance P receptors in primary cultures of cortical astrocytes from the mouse.

“…Since these studies did not exclude a localization of these binding sites on astrocytes as well, we investigated the possibility of SP receptors on astrocytes of newborn mice in primary culture. Indeed, receptors for several neurotransmitters or neurohormones have already been found on astrocytes using binding and electrophysiological techniques (13)(14)(15)(16), the determination of adenylate cyclase activity on membranes (17,18), or the measurement of cAMP, cGMP (19)(20)(21), and inositol phosphates in intact cells (22,23). In addition, SP was shown to amplify the increase in cAMP accumulation evoked by norepinephrine in purified astrocytes (24).…”

Biased inhibition by a suramin analogue of A 1 -adenosine receptor/G protein coupling in fused receptor/G protein tandems: the A 1 -adenosine receptor is predominantly coupled to Go α in human brain

“…Thus, the vast excess concentrations of Gα i cannot efficiently compete with Gα o (or with the mutants) and invade the tandem when the first complex is being formed. The A 1 -adenosine receptor is widely distributed in the brain and a large proportion of neurons express this receptor subtype (Haas and Selbach 2000); in addition, glial cells are also endowed with A 1 -adenosine receptors (van Calker et al 1980). It is therefore conceivable and reasonably probable that additional G proteins also participate in delayed signalling by the A 1 -adenosine receptor.…”