ISSN:
1573-6830
Keywords:
peptides
;
adenosine receptors
;
adrenergic receptors
;
serotonin receptors
;
guanyl nucleotide exchange
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
Notes:
Summary 1. Adenoregulin is an amphilic peptide isolated from skin mucus of the tree frog,Phyllomedusa bicolor. Synthetic adenoregulin enhanced the binding of agonists to several G-protein-coupled receptors in rat brain membranes. 2. The maximal enhancement of agonist binding, and in parentheses, the concentration of adenoregulin affording maximal enhancement were as follows: 60% (20 µM) for A1-adenosine receptors, 30% (100 µM) for A2a-adenosine receptors, 20% (2 µM) forα 2-adrenergic receptors, and 30% (100 µM) for 5HT1A receptors. High affinity agonist binding for A1-,α 2-, and 5HT1A-receptors was virtually abolished by GTPγS in the presence of adenoregulin, but was only partially abolished in its absence. Magnesium ions increased the binding of agonists to receptors and reduced the enhancement elicited by adenoregulin. 3. The effect of adenoregulin on binding of N6-cyclohexyladenosine ([3H]CHA) to A1-receptors was relatively slow and was irreversible. Adenoregulin increased the Bmax value for [3H]CHA binding sites, and the proportion of high affinity states, and slowed the rate of [3H]CHA dissociation. Binding of the A1-selective antagonist, [3H]DPCPX, was maximally enhanced by only 13% at 2 µM adenoregulin. Basal and A1-adenosine receptor-stimulated binding of [35S]GTPγS were maximally enhanced 45% and 23%, respectively, by 50 µM adenoregulin. In CHAPS-solubilized membranes from rat cortex, the binding of both [3H]CHA and [3H]DPCPX were enhanced by adenoregulin. Binding of [3H]CHA to membranes from DDT1 MF-2 cells was maximally enhanced 17% at 20 µM adenoregulin. In intact DDT1 MF-2 cells, 20 µM adenoregulin did not potentiate the inhibition of cyclic AMP accumulation mediatedvia the adenosine A1 receptor. 4. It is proposed that adenoregulin enhances agonist binding through a mechanism involving enhancement of guanyl nucleotide exchange at G-proteins, resulting in a conversion of receptors into a high affinity state complexed with guanyl nucleotide-free G-protein.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02071881
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