Comparative molecular biological studies on the vasoactive peptide receptors.

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To further advance our understanding on the physiological significance of vasoactive peptides, we carried out the following comparative molecular biological studies on their receptors.1) Natriuretic peptide receptors : The intra-and inter-subunit disulfide bonding pattern of the bovine and eel natriuretic peptide receptor C (NPR-C) were determined by a combination of protein sequencing and site-directed mutagenesis. Analysis of the cDNA and gene structures of mammalian NPR-C revealed the presence of an alternatively spliced mRNA species that encodes a receptor protein with a slightly modified sequence in the juxta-membrane region of the extracellular domain. A new receptor subtype, termed NPR-D,has been identified, cloned, and characterized. NPR-D has a short cytoplasmic tail and is 70% similar to the NPR-C sequence, but quite different in the tissue distribution ; NPR-D is abundant in the brain.2)Endothelin receptors : Localization of the endothelin receptor B (ET-B) was determined by immunohistochemistry and the vascular endotherium was found to be decorated most densely. Type A endothelin receptor (ET-A) was found to be highly expressed in the perichondrium of rats and the gill epitherium of trout, suggesting that endothelin is involved in the differentiation of chondrocytes and regulation of gill functions.