Effects of C‐Type Natriuretic Peptide on Rat Astrocytes: Regional Differences and Characterization of Receptors

Abstract

We have compared the effects of atrial natriuretic peptide (ANP), brain natriuretic peptide (BMP), and C‐type natriuretic peptide (CNP) on the accumulation of cyclic GMP (cGMP) in secondary cultures of rat astro‐cytes. The order of potency of these peptides was CNP < ANP < BNP, which would be compatible with a predominance of guanylate cyclase B (GC‐B)‐versus guanylate cyclase A (GC‐A)‐type receptors in these cells. Accordingly, we found by northern blot analysis that the mRNA transcripts of GC‐B were much more abundant in astro‐cytes than the transcripts of GC‐A. In addition, astrocytes from diencephalon accumulated two times more cGMP in response to CNP than astrocytes from cortex. Binding experiments with 125l‐labeled ANP or [Tyr0]‐CNP established that these ligands recognized only clearance‐type receptors on astrocytes. However, the number of binding sites was ∼ 100 times higher in astrocytes from cortex than in astrocytes from diencephalon and thus was inversely correlated to the amplitude of the cGMP response in the same cells. We found no further evidence for differences in the levels of GC‐B receptors in astrocytes from the two regions because (a) the abundance of GC‐B mRNA was similar and (b) there was no difference in particulate guanylate cyclase activity in astrocytes from each region. In addition, occupancy of clearance receptors with C‐ANP4–23 did not affect the accumulation of cGMP in response to CNP; this makes it unlikely that the differences in cGMP responsiveness can be accounted for by binding and sequestration of CNP to the clearance receptors. Thus, the abundance of GC‐B receptors is not the only factor governing the amounts of cGMP they can generate on exposure to CNP. Other factors may regulate the ability of these receptors to generate cGMP in astrocytes.

ANP-mediated cGMP signaling and phosphodiesterase inhibition in the rat cervical spinal cord

“…In addition, we observed ANP-stimulated cGMP synthesis in astrocytes in all gray matter layers, and also in the dorsal and lateral white matter columns. These observations are in agreement with our previous observations (Vles et al, 2000) and reports by others (Deschepper and Picard, 1994;De Vente et al, 1989, 1990Friedl et al, 1989;Hösli and Hösli, 1992). The effect of NPs on cGMP synthesis in astrocytes of the spinal cord is variable from one experiment to the other.…”

Retinal degeneration protein 3 controls membrane guanylate cyclase activities in brain tissue

“…Therefore, inhibition of GC-A or GC-B by RD3 in brain tissue might be a critical regulatory feature. We observed stimulation of GC activities by ANP and CNP in astrocytes ( Figure 3B ) that was broadly consistent with a previous investigation that correlates ligand binding to cGMP accumulation by ANP and CNP ( Deschepper and Picard, 1994 ). We here show that RD3 inhibited both GCs in astrocytes demonstrating that RD3 can exert its effects in a primary cell culture.…”

Dexamethasone increases production of C-type natriuretic peptide in the sheep brain

“…In further support of a CNP-specific action of dexamethasone in central tissues, the expression of the ANP and BNP receptor, NPR1, was also unaffected. Concerning possible actions of CNP in glial tissues, there is a strong body of evidence 235:1 that cGMP, a downstream mediator of CNP activity and more responsive to CNP than either ANP or BNP (Deschepper & Picard 1994), regulates several crucial intercellular actions including Na + /H + exchangers, neurotransmitter re-uptake, gap junctions, cell pH and brain cell water content (Kim et al 2010). In this context, it is important to note that dexamethasone mitigates cerebral glioma tumour oedema, a cell type highly responsive to CNP (Eguchi et al 1992, Wu et al 2017.…”