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  • Title: ATP-sensitive and maxi potassium channels regulate BRL 37344-induced tocolysis in buffaloes-an in vitro study.
    Author: Sharma V, Nair SV, Jaitley P, Nakade UP, Sharma A, Choudhury S, Garg SK.
    Journal: Theriogenology; 2018 Feb; 107():194-202. PubMed ID: 29172176.
    Abstract:
    Cellular coupling of beta3-adrenoceptors (β3-ADR) to potassium channels in myometrium is largely unknown. In vitro study was undertaken to unravel the presence of β3-adrenergic receptors (ADR) and the role of K+-channels in mediating β3-ADR-induced relaxation in isolated myometrial strips from cyclic non-pregnant water buffaloes. Isometric tension was recorded in isolated myometrial strips using data acquisition system based physiograph. Compared to SR 59230A, BRL 37344 was found to be more potent in inducing β3-dependent myometrial relaxation which was significantly (p < 0.05) inhibited in the presence of β3 antagonist, SAR 150640. The immunoreactive protein to β3-ADR was also detected in membrane fraction of myometrial protein. Further, incubation with BRL 37344 (10 μM) significantly (p < 0.05) increased c-AMP accumulation (37.58 ± 9.52 pmol/mg protein; n = 4) in the myometrial strips compared to basal c-AMP level (16.85 ± 3.87 pmol/mg protein; n = 4). The concentration response curves (CRC) of BRL 37344 were significantly (p < 0.05) shifted towards right in the presence of KATP channels specific blocker, glibenclamide (10 μM) and maxi K+-channels (BKCa) specific blocker, iberiotoxin (100 nM), with decrease in both efficacy and potency as compared to control. However, 4-aminopyridine (4-AP), a specific blocker of the voltage gated K+-channels (Kv), failed to alter the CRC of BRL 37344. Existence of immunoreactive protein to Kir6.1, α-subunit of BKCa and Kv1.1 channels were also detected in the membrane fraction of myometrial protein. Based on the above findings, it can be concluded that BRL 37344 is a potent stimulator of β3-adrenoceptors in buffalo myometrium and besides mediating their effect through rise in c-AMP, they are coupled to KATP and BKCa channels in inducing tocolytic effects.
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