Adrenomedullin receptors in rat cerebral microvessels

To characterize the sites of action of adrenomedullin (AM) in the cerebral microvasculature, we studied the effect of AM on cyclic AMP (cAMP) level as well as expression of AM and its receptor in the rat cerebral microvessels . The microvessels were prepared from rat cerebral cortex by albumin flotat ion and glass bead filtration technique. AM and calcitonin gene-related pep tide (CGRP) increased cAMP level in the microvessels in a concentration-dep endent manner. The effect of AM was more than 100 times more potent than th at of CGRP. The accumulation of cAMP by AM was inhibited by AM[22-52], an A M receptor antagonist, but not by CGRP[8-37], a CGRP receptor antagonist, s uggesting that AM increased cAMP accumulation by acting on receptors specif ic to AM. [I-125]AM binding to the microvessels was displaced by AM and les s potently by AM[22-52]. The displacing potencies of CGRP and CGRP[8-37] we re very weak. mRNAs for AM as well as calcitonin-receptor-like receptor and receptor-activity-Modifying protein 2 which form a receptor specific to AM , were highly expressed in the microvessels. These results provide biochemi cal and pharmacological evidence that AM is produced in and acts on the cer ebral microvessels in an autocrine/paracrine manner and is involved in regu lation of cerebral microcirculation. (C) 2000 Elsevier Science B.V. All rig hts reserved.