Parathyrin and calcitonin stimulate cyclic AMP accumulation in cultured murine brain cells.

Abstract

Despite the key role Ca2+ plays in the nervous system, biochemical actions on neural tissue of the Ca2+‐regulating peptide hormones parathyrin and calcitonin were unknown. Until a few years ago only neurons, but not glial cells, were considered as targets for peptide hormones. Our recent observation that peptide hormones do indeed act on glial cells is extended by the present report that these cells respond to the calcaemic peptide hormones parathyrin and calcitonin. In cultured murine brain cells mainly consisting of glioblasts, parathyrin stimulates the accumulation of cyclic AMP. The half‐maximal effect is elicited at 30 nM parathyrin. With rat brain cells the effects are three times those observed with mouse brain cells. Calcitonin, which is less potent than parathyrin, elevates the concentration of cyclic AMP only in rat brain cells. If properly occupied, the inhibitory receptors present on the cells lower the increase in the level of cyclic AMP evoked by parathyrin and, to some extent, that elicited by calcitonin. The results suggest that: (i) these or closely related hormones might exert regulatory functions in brain; and (ii) glial cells must be considered in discussions of the targets of the calcaemic and other peptide hormones.

Corticotropin Peptides and Melanotropins Elevate the Level of Adenosine 3′: 5′‐Cyclic Monophosphate in Cultured Murine Brain Cells

“…In murine brain cell cultures consisting essentially of glial cells the predominant cell type is of astroglial character, as demonstrated by the presence of appropriate markers (Bock et al, 1975;1977;Hallermayer et al, 1981). Several hormones have previously been shown to regulate, positively or negatively, the intracellular concentration of cyclic AMP in such cultures (van Calker et al, 1978u,h;Loffler et al, 1982). And as reported here, peptides of the ACTH/MSH family elevate cyclic AMP levels.…”

“…Cells were cultured for 11 days. Protein per plate = 0.9 mg. Loffler et al, 1982). Thus the aand j3-adrenergic antagonists phentolamine and propranolol and the secretin antagonist secretin-(5-27) (Robberecht et al, 1976;Propst et al, 1979) do not influence the actions of ACTH and MSH (data not shown).…”

“…(18 -39) (corticotropin-like intermediate lobe peptide, CLIP), y-MSH (Nakanishi et al, 1979: identical with y,-MSH of Ling et al, 1979) and human P-MSH, Penin-ACTH-(1-lo), ACTH-(4-10), ACTH-(4-11), ACTH-sula, San Carlos, California, U.S.A. The sources of all other materials are given elsewhere (van Calker et al, 1978a;: Propst et al, 1979Loffler et al, 1982).…”

“…calcaemic hormones parathyrin and calcitonin (Loffler et al, 1982) were among the stimulating hormones, somatostatin (Propst et al, 1979; among the inhibitory ones.…”

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).…”