Activation of human 5-hydroxytryptamine type 3 receptors via an allosteric transmembrane site.

Activation of human 5-HT3 receptors via an allosteric transmembrane site

Nicotinic acetylcholine receptor transmembrane mutations convert ivermectin from a positive to a negative allosteric modulator.

Ivermectin is a macrocyclic lactone that acts as a positive allosteric modulator of alpha7 nicotinic acetylcholine receptors (nAChRs) but has no modulatory activity on 5-hydroxytryptamine (5-HT) type 3 (5-HT(3)) receptors. By examining the influence of ivermectin on subunit chimeras containing domains from the nAChR alpha7 subunit and the 5-HT3A subunit, we have concluded that the transmembrane...

Agonist activation of alpha7 nicotinic acetylcholine receptors via an allosteric transmembrane site.

Conventional nicotinic acetylcholine receptor (nAChR) agonists, such as acetylcholine, act at an extracellular "orthosteric" binding site located at the interface between two adjacent subunits. Here, we present evidence of potent activation of α7 nAChRs via an allosteric transmembrane site. Previous studies have identified a series of nAChR-positive allosteric modulators (PAMs) that lack agonis...

Unique allosteric regulation of 5-hydroxytryptamine receptor-mediated signal transduction by oleamide.

The effects of oleamide, an amidated lipid isolated from the cerebrospinal fluid of sleep-deprived cats, on serotonin receptor-mediated responses were investigated in cultured mammalian cells. In rat P11 cells, which endogenously express the 5-hydroxytryptamine2A (5HT2A) receptor, oleamide significantly potentiated 5HT-induced phosphoinositide hydrolysis. In HeLa cells expressing the 5HT7 recep...

A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivo.

Metabotropic glutamate receptor (mGluR) subtypes (mGluR1 to mGluR8) act as important pre- and postsynaptic regulators of neurotransmission in the CNS. These receptors consist of two domains, an extracellular region containing the orthosteric agonist site and a transmembrane heptahelical domain involved in G protein activation and recognition of several recently synthesized pharmacological modul...