Co-expression of prepro-adrenomedullin with a putative adrenomedullin receptor gene in vascular smooth muscle.
The prepro-adrenomedullin (prepro-AM) gene encodes several biologically active peptides, including the potent vasodilator AM. At least part of the vasodilator action of AM appears to be mediated via interactions with receptors on vascular smooth muscle cells (VSMC); however, the specific receptors involved are not known. The aim of the present study was to identify putative AM receptor genes that are co-expressed with AM in cultured rat aortic VSMC that may mediate the actions of AM. AM mRNA was shown to be expressed in rat aortic VSMC cultures. In acute (4 h) secretion studies, only 20% of the total immunoreactive AM was intracellular, with the majority (80%) found in the medium, indicating active release of AM peptide from VSMC. Using highly specific ribonuclease protection analysis, mRNAs encoding three putative AM receptors [L1, calcitonin-receptor-like receptor (CRLR) and RDC1] were shown to be present at high concentrations in RNA extracts from lung. In cultured VSMC, however, whereas RDC1 mRNA was expressed at relatively high concentrations, transcripts encoding CRLR and L1 were not detected. The co-expression of prepro-AM mRNA with the RDC1 receptor implies that AM may act in a localized manner via this receptor to modulate VSMC function.
Autelitano
D J
DJ
Molecular Physiology Laboratory, Baker Medical Research Institute, P. O. Box 6492, Melbourne, Victoria 8008, Australia.
Tang
F
F
D053607:Adrenomedullin; D000818:Animals; D001011:Aorta; D058286:Calcitonin Receptor-Like Protein; D046508:Culture Techniques; D015870:Gene Expression; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry*; D010455:Peptides / Q000032:analysis; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin / Q000235:genetics; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000235:genetics; D018000:Receptors, Peptide; D020133:Reverse Transcriptase Polymerase Chain Reaction
D058286:Calcitonin Receptor-Like Protein; C545580:Calcrl protein, rat; D008565:Membrane Proteins; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D058265:Receptors, Adrenomedullin; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; D018000:Receptors, Peptide; C112034:preproadrenomedullin; D053607:Adrenomedullin