{'fraction_non_alphanumeric': 0.04192439862542955, 'fraction_numerical': 0.03367697594501718, 'mean_word_length': 5.3304347826086955, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Adenosine A1 receptor signaling inhibits BK channels

Adenosine receptor (AR) contracts and relaxes mouse aorta through all four subtypes (A1, A2A, A2B, and A3) linked to different signaling mechanisms. Deciphering complex tissue responses remains difficult because relationships of individual receptor subtypes and various end‐effectors (e.g., ion channels) are yet to be identified. A1AR is linked to cytochrome P450 4a (Cyp4a), an enzyme producing 20‐HETE from arachidonic acid. 20‐HETE can inhibit large conductance Ca2+/voltage‐sensitive K+ (BK) channels that are important in adenosine‐induced smooth muscle relaxation. We tested the hypothesis that activation of A1AR blunts adenosine‐induced vascular relaxation by coupling 20‐HETE production to inhibition of BK channels. Patch clamp recordings and Western blots were conducted by using wild type (WT) and A1AR knockout (A1KO) mice aortic myocytes. We observed no difference in total BK current or BK channel proteins (BK‐α and BK‐β1) in aortic myocytes from WT and A1KO mice. Non‐selective adenosine agonist NECA (10 μM) increased BK current in myocytes from both WT and A1KO mice, but had greater response in aortic myocytes from A1KO mice (p < 0.05). 20‐HETE (100 nM) inhibited BK current in myocytes from WT and A1KO mice and no difference was observed in the inhibition. Our data suggest that A1AR limits adenosine‐induced vascular relaxation by inhibiting BK channels. (HL027339, HL094447).