Atrial natriuretic peptide induces rat peritoneal mast cell activation by cGMP-independent and calcium uptake-dependent mechanism

Abstract

Atrial natriuretic peptide (ANP), a 28 amino acid basic polypeptide, is known to induce histamine release from human and rat mast cells in vitro and cause a wheel formation in rat skin. However, cellular events associated with histamine release are not clearly understood. In this study, we have examined the calcium flux and cGMP formation associated with histamine release in the ANP-treated mast cells. ANP, in vitro, induced mast cell degranulation and histamine release in a dose-dependent manner. ANP also induced an enhanced calcium uptake into cells and increased the cellular level of cGMP in mast cells. A high level of calcium in the media caused an inhibition of ANP-dependent histamine release but enhanced the level of intracellular cGMP of mast cells. ANP inducing a dose-dependent increase in vascular permeability of rat skin was confirmed by the extravasation of the circulating Evans blue. The results indicate ANP induced the histamine release and an increase in vascular permeability through mast cell degranulation in cGMP-independent and calcium uptake-dependent manner.

Atrial Natriuretic Peptide–Mediated Inhibition of Microcirculatory Endothelial Ca 2+ and Permeability Response to Histamine Involves cGMP-Dependent Protein Kinase I and TRPC6 Channels

“…Contradicting our results, it was reported that ANP itself can activate mast cells isolated from peritoneum or placenta, with the former being mediated via a GC-A/cGMP-independent pathway. 37,38 In contrast, ANP does not induce degranulation of isolated rodent cardiac mast cells. 39 Therefore, it seems that there is variability in the actions of ANP on mast cells isolated from different organs.…”

Natriuretic peptides and genesis of asthma: An emerging paradigm?☆

“…7,39 Also, ANP induces mast cells to release histamine, an important mediator of allergic inflammation. 40,41 ANP acts on epithelial cells to produce TGF-b 1 , which is involved in the genesis of pulmonary fibrosis, a characteristic of remodeled lung. ANP enhances human NK T cells, 42 which are crucial to the development of airway hyperreactivity.…”

Response of cardiac mast cells to atrial natriuretic peptide

“…It was concluded that this elevation in the myocardial natriuretic system was an adaptational, autocrine/paracrine response responsible for regulating cardiac remodeling (1,17,19,22,26). ANP, which has been shown to cause degranulation in noncardiac mast cells (10,29,39), was originally identified as a member of a family of three separate peptide neurohormones, Fig. 2.…”

“…Chronic volume overload (CVO) has been shown to induce rapid expression of atrial natriuretic peptide (ANP) mRNA and protein in cardiac tissue, as well as natriuretic peptide receptors (NPRs) (3,22,31,35). Furthermore, ANP has been shown to cause degranulation in noncardiac mast cells (10,29,39). However, it is not known whether ANP activates cardiac mast cells.…”