Dibutyryl‐cyclic GMP induces peripheral antinociception via activation of ATP‐sensitive K+ channels in the rat PGE2‐induced hyperalgesic paw

• Published in: British journal of pharmacology Vol. 134; no. 1; pp. 127 - 131
• Main Authors: Soares, A C, Duarte, I D G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2001; Nature Publishing
• Subjects: 4-Aminopyridine - pharmacology; Adenosine Triphosphate - physiology; Analgesics; Analgesics - pharmacology; Animals; antinociception; Apamin - pharmacology; Biological and medical sciences; Cesium - pharmacology; Charybdotoxin - pharmacology; DbcGMP; Dibutyryl Cyclic GMP - pharmacology; Dinoprostone - administration & dosage; Dose-Response Relationship, Drug; glibenclamide; Glyburide - pharmacology; Hindlimb - drug effects; Hindlimb - pathology; Hyperalgesia - chemically induced; Hyperalgesia - prevention & control; K+ channel blockers; Male; Medical sciences; morphine; Neuropharmacology; Pain - prevention & control; Pain Measurement; Pain Threshold - drug effects; Pharmacology. Drug treatments; Potassium Channels - drug effects; Potassium Channels - metabolism; Rats; Rats, Wistar; Tetraethylammonium - pharmacology; Tolbutamide - pharmacology; Nociception; Prostaglandin; Rat; Potassium channel antagonist; Arachidonic acid derivatives; Rodentia; Prostaglandin E2; 3',5'-GMP; Ionic channel; Biological activity; Vertebrata; Cholinergic receptor; Mammalia; Analgesic; Analog; Animal; Mechanism of action; Potassium
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0704224

Using the rat paw pressure test, in which increased sensitivity is induced by intraplantar injection of prostaglandin E2, we studied the action of several K+ channel blockers in order to determine what types of K+ channels could be involved in the peripheral antinociception induced by dibutyrylguanosine 3 : 5′‐cyclic monophosphate (DbcGMP), a membrane permeable analogue of cyclic GMP.
DbcGMP elicited a dose‐dependent (50, 75, 100 and 200 μg paw−1) peripheral antinociceptive effect. The effect of the 100 μg dose of DbcGMP was considered to be local since only a higher dose (300 μg paw−1) produced antinociception in the contralateral paw.
The antinociceptive effect of DbcGMP (100 μg paw−1) was dose‐dependently antagonized by intraplantar administration of the sulphonylureas tolbutamide (20, 40 and 160 μg) and glibenclamide (40, 80 and 160 μg), selective blockers of ATP‐sensitive K+ channels.
Charybdotoxin (2 μg paw−1), a selective blocker of high conductance Ca2+‐activated K+ channels, and apamin (10 μg paw−1), a selective blocker of low conductance Ca2+‐activated K+ channels, did not modify the peripheral antinociception induced by DbcGMP.
Tetraethylammonium (2 mg paw−1), 4‐aminopyridine (200 μg paw−1) and cesium (800 paw−1), non‐selective voltage‐gated potassium channel blockers, also had no effect.
Based on this experimental evidence, we conclude that the activation of ATP‐sensitive K+ channels could be the mechanism by which DbcGMP induces peripheral antinociception, and that Ca2+‐activated K+ channels and voltage‐dependent K+ channels appear not to be involved in the process.
British Journal of Pharmacology (2001) 134, 127–131; doi:10.1038/sj.bjp.0704224