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. 1990 Sep;101(1):115–120. doi: 10.1111/j.1476-5381.1990.tb12099.x

Phentolamine and yohimbine inhibit ATP-sensitive K+ channels in mouse pancreatic beta-cells.

T D Plant 1, J C Henquin 1
PMCID: PMC1917617  PMID: 2282453

Abstract

1. The effects of phentolamine and yohimbine on adenosine 5'-triphosphate (ATP)-sensitive K+ channels were studied in normal mouse beta-cells. 2. In the presence of 3 mM glucose, many ATP-sensitive K+ channels are open in the beta-cell membrane. Under these conditions, phentolamine inhibited 86Rb efflux from the islets. This inhibition was faster with 100 than with 20 microM phentolamine but its steady-state magnitude was similar with both concentrations. Yohimbine (20-100 microM) also inhibited the efflux rate but was not as potent as phentolamine. 3. In the presence of 6 mM glucose, most ATP-sensitive K+ channels are closed in the beta-cell membrane. Their opening by 100 microM diazoxide caused a marked acceleration of 86Rb efflux from the islets. This acceleration was almost entirely prevented by 20 microM phentolamine. It was barely affected by 20 microM yohimbine and reduced by 50% by 100 microM yohimbine. 4. ATP-sensitive K+ currents were studied in single beta-cells by the whole cell patch-clamp technique. Phentolamine (20-100 microM) caused a progressive but almost complete and irreversible inhibition of the current. The effects of yohimbine were faster but smaller; the inhibition was still incomplete with 100 microM yohimbine. 5. The increase in ATP-sensitive K+ current produced by 100 microM diazoxide was prevented by 100 microM phentolamine but only partially attenuated by 100 microM yohimbine. 6. It is concluded that phentolamine inhibits ATP-sensitive K+ channels in pancreatic beta-cells. This novel effect of phentolamine resembles that of hypoglycaemic sulphonylureas. It may account for previously unexplained effects of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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