PAXILLINE

Description

A complex alkaloid, paxilline occurs in the mycelium of the mold Penicillium paxilli. The structure has been confirmed by X-ray crystallography. The crystals are orthorhombic with space group P2 12 121 and a = 31.009, b = 11.522 and c = 7.70 A.

Description

Paxilline is an indole diterpene from fungi which potently and reversibly inhibits large conductance Ca²⁺-activated K⁺ (BKCa) channels, as shown in patch clamp (K_i = 1.9 nM) and whole smooth muscle cell studies (K_i = 35.7 nM). It also enhances the binding of charybdotoxin , a peptidyl neurotoxin, to BKCa channels. Paxilline is currently used to evaluate the role of BKCa channels in various cell processes and responses.

Chemical properties

Powder

The Uses of PAXILLINE

Paxilline is a tremorgenic mycotoxin isolated from species of Penicillium, Acremonium and Emericella. Paxilline selectively blocks high-conductance Ca2+-activated potassium channels and inhibits binding to the cerebellar inositol 1,4,5-triphosphate (InsP(3)) receptor.

The Uses of PAXILLINE

Potent blocker of high-conductance calcium-activated potassium (BKCa) channels

What are the applications of Application

Paxilline is a selective and reversible calcium-activated potassium channel blocker

Definition

ChEBI: Paxilline is an indole diterpene alkaloid with formula C27H33NO4 isolated from Penicillium paxilli. It is a potent inhibitor of large conductance Ca2(+)- and voltage-activated K(+) (BK)-type channels. It has a role as a mycotoxin, a Penicillium metabolite, an anticonvulsant, an Aspergillus metabolite, a potassium channel blocker, a genotoxin, a geroprotector and an EC 3.6.3.8 (Ca(2+)-transporting ATPase) inhibitor. It is an organic heterohexacyclic compound, a tertiary alcohol, a terpenoid indole alkaloid, an enone and a diterpene alkaloid.

Biological Activity

Potent blocker of high-conductance Ca 2+ -activated K + (BK Ca ) channels. Binds to the α -subunit of BK Ca (K i = 1.9 nM for block of currents in α -subunit-expressing oocytes) and enhances binding of charybdotoxin to BK Ca channels in vascular smooth muscle. Also inhibits sarco/endoplasmic reticulum Ca 2+ -ATPase (IC 50 = 5-50 μ M).

Enzyme inhibitor

This BKCa/KCa1.1) channel blocker (FW = 435.56 g/mol; CAS 57186-25-1; Solubility: 100 mM in DMSO), also named (2R,4bS,6aS,12bS,12cR,14aS)- 5,6,6a,7,12,12b,12c,13,14,14a-decahydro-4b-hydroxy-2-(1-hydroxy-1- methylethyl)-12b,12c-dimethyl-2H-pyrano[2'',3'': 5',6']benz[1',2':6,7]indeno [1,2-b]indol-3(4bH)-one, binds to the α-subunit of BKCa, exhibiting a Ki value of 1.9 nM in blocking currents in α-subunit-expressing oocytes and enhancing binding of to BKCa channels in vascular smooth muscle. (See Charybdotoxin) Paxilline also inhibits sarco/endoplasmic reticulum Ca2+-ATPase, IC50 = 5 - 50 μM.

storage

-20°C (desiccate)

References

Springer et ai., Tetrahedron Lett., 2531 (1975)