Marabita and Islam demonstrated that human [beta]-cells express at least eight TRP channels, for example, TRPC1, TRPM4, TRPM7, TRPM2, TRPM3, TRPP2, TRPML1, and TRPML3 .
Although 9-phenanthrol was initially discovered as an inhibitor of the TRPM4 channels, later studies showed that it also inhibits the transmembrane protein 16A (TMEM16A), a [Ca.sup.2+]-activated [Cl.sup.-] channel .
The fact that 20-30 [micro]M 9phenanthrol inhibited insulin secretion is consistent with the fact that the inhibition of insulin secretion was due to the inhibition of the TRPM4 channels because the IC50 of 9-phenanthrol for the transfected or the endogenous TRPM4 channels has been shown to be 20-30 [micro]M in many cells [5, 6].
As mentioned earlier, this channel is also inhibited by 9-phenanthrol at similar concentrations that inhibit the TRPM4 channel .
We have demonstrated that 9-phenanthrol, an inhibitor of the TRPM4 and the TMEM16A channels and an activator of the [K.sub.ca]3.1 channel, strongly inhibits both the glucose-and the GLP-1-induced insulin secretion.
Del Negro, "The TRPM4 channel inhibitor 9-phenanthrol," British Journal of Pharmacology, vol.
Norez et al., "9-phenanthrol inhibits human TRPM4 but not TRPM5 cationic channels," British Journal of Pharmacology, vol.