Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:037242 (SUR1)
 879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of a novel vasorelaxant agent, MCC-134 (1-[4-(1H-imidazol-1-yl)benzoyl]-N-methyl-cyclobutanecarbothioamide++ +), were examined on reconstituted ATP-sensitive K(+) (K(ATP)) channels, which are composed of an inwardly rectifying K(+) channel, Kir6.2, and three types of sulfonylurea receptors (SUR): SUR1, SUR2A, and SUR2B. Each type of K(ATP) channel was heterologously expressed in human embryonic kidney 293T cells. The expressed K(ATP) channel currents were measured with the whole-cell configuration of the patch-clamp method. MCC-134 activated the SUR2B/Kir6.2 channel, was a weak activator of the SUR2A/Kir6.2 channel, but did not activate the SUR1/Kir6.2 channel. MCC-134 suppressed SUR1/Kir6.2 channel currents that had been fully activated by either diazoxide or NaCN, whereas it did not affect the fully activated SUR2A/Kir6.2 or SUR2B/Kir6.2 channel currents. Thus, MCC-134, which is a relatively effective opener of the vascular smooth muscle type (SUR2B) of K(ATP) channel, is an antagonist of the pancreatic type (SUR1) of K(ATP) channel. Therefore, depending on the subtype of SUR, a pharmacological agent can cause either activation or inhibition of K(ATP) channel activity.
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PMID:MCC-134, a novel vascular relaxing agent, is an inverse agonist for the pancreatic-type ATP-sensitive K(+) channel. 1060 39

(1) We have investigated the possible roles of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP-sensitive K(+) channels (K(ATP) channels) by use of patch-clamp and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques. (2) In voltage-clamp experiments, not only diazoxide, a SUR1 and weak SUR2B activator, but also pinacidil, a selective SUR2 activator, caused an inward current at a holding potential of -50 mV in symmetrical 140 mM K(+) conditions. (3) Gliclazide (</=1 micro M), a selective SUR1 blocker, inhibited the 10 micro M pinacidil-induced currents (K(i)=177 micro M) and the 500 micro M diazoxide-induced currents (high-affinity site, K(i1)=5 nM; low-affinity site, K(i2)=108 micro M) at -50 mV. (4) Application of tolbutamide (</=100 micro M) reversibly caused an inhibition of the 500 micro M diazoxide-induced current at -50 mV. (5) MCC-134, a SUR type-specific K(ATP) channel regulator (1-100 micro M), produced a concentration-dependent inward K(+) current, which was suppressed by the application of glibenclamide at -50 mV. The amplitude of the MCC-134 (100 micro M)-induced current was approximately 50% of that of the 100 micro M pinacidil-induced currents. (6) Using cell-attached configuration, MCC-134 activated a glibenclamide-sensitive K(ATP) channel which was also activated by pinacidil. (7) RT-PCR analysis demonstrated the presence of SUR1 and SUR2B transcripts in pig urethra. 8 These results indicate that both SUR1 and SUR2B subunits play a functional role in regulating the activity of pig urethral K(ATP) channels and that SUR1 contributes less than 25% to total K(ATP) currents.
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PMID:Functional involvement of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP-sensitive K+ channels. 1278 25