Adrenomedullin receptor binding sites in rat brain and peripheral tissues.

The existence of specific adrenomedullin receptor binding sites was investigated using the agonist peptide fragment [125I]human adrenomedullin-(13-52) in rat brain, lung and vas deferens homogenates. Saturation-binding experiments suggest that [125I]human adrenomedullin-(13-52) binds to an apparent single population of sites with similar affinities (K(D) of 0.3 to 0.

Autoradiographic distribution of adrenomedullin receptors in the rat brain.

The autoradiographic distribution of putative brain adrenomedullin receptors was investigated using [125I]human adrenomedullin(13-52) as a new radioligand. Specific [125I]human adrenomedullin(13-52) binding sites were very discretely distributed in the rat brain with enrichment seen in the choroid plexus and linings of the third, fourth and lateral ventricles, basolateral amygdaloid nuclei, neural lobe of the pituitary gland, the trigeminal nerves and in the granular cell layer of the cerebellum. To our knowledge, this is the first report on the discrete localization of adrenomedullin receptors in the mammalian brain.

CCK mRNA expression in neuroendocrine CRH neurons is increased in rats subjected to an immune challenge.

The expression of cholecystokinin (CCK) mRNA in neuroendocrine corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN) of male rats was examined 8 h following an acute immune challenge by intraperitoneal lipopolysaccharide (LPS, 250 microg/kg). Both quantitative, macroautoradiographic, single-label radioactive in situ hybridization histochemistry (ISHH) and qualitative dual-label ISHH were performed. Compared to controls, LPS-injected rats displayed increased (185%) parvicellular CCK mRNA expression levels, occurring in a majority (70%) of CRH neurons as revealed by dual-label ISHH.

The molecular pharmacology of CGRP and related peptide receptor subtypes.

Calcitonin gene-related peptides (alpha and beta isoforms), better known as CGRPalpha and CGRPbeta, were isolated twenty years ago. In fact, these were the first peptides to be characterized using a molecular cloning strategy, which is not the traditional approach of biochemical extraction and purification. Paradoxically, progress in the characterization of CGRP receptor subtypes has been extremely slow as a result of difficulties in their cloning and the lack of selective receptor subtype agonists and antagonists.

Glucocorticosteroids up-regulate the expression of cholecystokinin mRNA in the rat paraventricular nucleus.

Adrenalectomy abolishes corticosteroid feedback onto the hypothalamic-pituitary-adrenal axis. This results in an increased biosynthetic and secretory activity of corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN), sustained in the absence of hormone replacement. In the PVN, cholecystokinin (CCK) is present both in parvicellular CRH-containing and in magnocellular oxytocin (OXY)-containing neurons.