Endocrine Abstracts

Adrenomedullin (ADM) is a multifunctional peptide which plays a significant role in vasodilation, angiogenisis and septic shock. It exerts its effects via the calcitonin receptor-like receptor (CRLR) in combination with either receptor associated protein (RAMP) 2 or 3. However the regulation of the ADM receptors is still widely unknown (1). In the present study the effects of adrenomedullin on immortalized Human Microvascular Endothelial Cells (HMECs) was investigated. Endothelial cells are well established as a model for the study of ADM actions. We found for the first time in this cell line the expression of ADM receptor message and protein using PCR and western blotting respectively. Treatment of the cells with ADM elevated intracellular cAMP levels in a dose (10(super)-6(/super)-10(super)-9(/super)M) and time (5-45min) dependent manner. However in this study, this did not result in increased cell proliferation. The consequences of the raised cAMP levels are yet to be established. We further investigated the possible transcriptional activation of the RAMPs and CRLR in response to ADM stimulation, using semi-quantitative PCR. The results suggest that after 24 hours treatment with ADM (10(super)-7(/super)M) the transcription of CRLR is increased. Taken together with the already published characterisation of the CRLR promoter (2) these findings provide an explanation for the regulation of the adrenomedullin receptors.

References:

1.Hinson JP, Kapas S, Smith DM 2000 Adrenomedullin, a Multifunctional Regulatory Peptide. Endocrine Reviews 21(2): 138-1672.

2. Nikitenko LL, Smith DM, Bicknell R, Rees MC 2003 Transcriptional Regulation of the CRLR gene in human microvascular endothelial cells by hypoxia. FASEB J. Aug 17(11):1499-501