Given an abstract from a research paper, your task is to identify and label relationships between chemical compounds and genes mentioned in the abstract.

The relationship type must be one of ['DOWNREGULATOR', 'SUBSTRATE', 'INDIRECT-REGULATOR', 'PART-OF', 'MODULATOR-ACTIVATOR', 'REGULATOR', 'INHIBITOR', 'COFACTOR', 'UPREGULATOR', 'ACTIVATOR', 'ANTAGONIST', 'NOT', 'INDIRECT-DOWNREGULATOR', 'SUBSTRATE_PRODUCT-OF', 'INDIRECT-UPREGULATOR', 'AGONIST', 'PRODUCT-OF', 'MODULATOR', 'DIRECT-REGULATOR', 'UNDEFINED', 'AGONIST-INHIBITOR', 'AGONIST-ACTIVATOR', 'MODULATOR-INHIBITOR'].

Please format your output as a JSON array. Each entry in the array should express a single relation, formatted as ["<Entity_A>", "<RELATION_A_B>", "<Entity_B>"]. If no relations can be found, please output an empty JSON array [].

Abstract:

Cerebrovascular Dilation via Selective Targeting of the Cholane Steroid-Recognition Site in the BK Channel β1-Subunit by a Novel Nonsteroidal Agent. The Ca (2+) /voltage-gated K (+) large conductance (BK) channel β1 subunit is particularly abundant in vascular smooth muscle. By determining their phenotype, BK β1 allows the BK channels to reduce myogenic tone, facilitating vasodilation. The endogenous steroid lithocholic acid (LCA) dilates cerebral arteries via BK channel activation, which requires recognition by a BK β1 site that includes Thr169. Whether exogenous nonsteroidal agents can access this site to selectively activate β1-containing BK channels and evoke vasodilation remain unknown. We performed a chemical structure database similarity search using LCA as a template, along with a two-step reaction to generate sodium 3-hydroxyolean-12-en-30-oate (HENA). HENA activated the BK (cbv1 + β1) channels cloned from rat cerebral artery myocytes with a potency (EC50 = 53 μM) similar to and an efficacy (×2.5 potentiation) significantly greater than that of LCA. This HENA action was replicated on native channels in rat cerebral artery myocytes. HENA failed to activate the channels made of cbv1 + β2, β3, β4, or β1T169A, indicating that this drug selectively targets β1-containing BK channels via the BK β1 steroid-sensing site. HENA (3-45 μM) dilated the rat and C57BL/6 mouse pressurized cerebral arteries. Consistent with the electrophysiologic results, this effect was larger than that of LCA. HENA failed to dilate the arteries from the KCNMB1 knockout mouse, underscoring BK β1 's role in HENA action. Finally, carotid artery-infusion of HENA (45 μM) dilated the pial cerebral arterioles via selective BK-channel targeting. In conclusion, we have identified for the first time a nonsteroidal agent that selectively activates β1-containing BK channels by targeting the steroid-sensing site in BK β1, rendering vasodilation.
[["Cholane", "DIRECT-REGULATOR", "BK Channel \u03b21-Subunit"], ["steroid", "REGULATOR", "BK channel"], ["HENA", "REGULATOR", "BK \u03b21"], ["LCA", "REGULATOR", "BK channel"], ["HENA", "DIRECT-REGULATOR", "BK-channel"], ["LCA", "DIRECT-REGULATOR", "BK \u03b21"], ["LCA", "ACTIVATOR", "BK (cbv1 + \u03b21) channels"], ["HENA", "ACTIVATOR", "\u03b21-containing BK channels"], ["HENA", "ACTIVATOR", "BK (cbv1 + \u03b21) channels"], ["lithocholic acid", "DIRECT-REGULATOR", "BK \u03b21"], ["HENA", "DIRECT-REGULATOR", "BK \u03b21"], ["lithocholic acid", "REGULATOR", "BK channel"], ["steroid", "DIRECT-REGULATOR", "BK \u03b21"]]