Isolation and pharmacological characterization of AdTx1, a natural peptide displaying specific insurmountable antagonism of the alpha1A-adrenoceptor.

ABSTRACT:

Background and purpose

Venoms are a rich source of ligands for ion channels, but very little is known about their capacity to modulate G-protein coupled receptor (GPCR) activity. We developed a strategy to identify novel toxins targeting GPCRs.

Experimental approach

We studied the interactions of mamba venom fractions with alpha(1)-adrenoceptors in binding experiments with (3)H-prazosin. The active peptide (AdTx1) was sequenced by Edman degradation and mass spectrometry fragmentation. Its synthetic homologue was pharmacologically characterized by binding experiments using cloned receptors and by functional experiments on rabbit isolated prostatic smooth muscle.

Key results

AdTx1, a 65 amino-acid peptide stabilized by four disulphide bridges, belongs to the three-finge

SUBMITTER: Quinton L 

PROVIDER: S-EPMC2825353 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature