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

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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.

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