Dibutyryl-cyclic GMP induces peripheral antinociception via activation of ATP-sensitive K(+) channels in the rat PGE2-induced hyperalgesic paw.
1. 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. 2. DbcGMP elicited a dose-dependent (50, 75, 100 and 200 microg paw(-1)) peripheral antinociceptive effect. The effect of the 100 microg dose of DbcGMP was considered to be local since only a higher dose (300 microg paw(-1)) produced antinociception in the contralateral paw. 3. The antinociceptive effect of DbcGMP (100 microg paw(-1)) was dose-dependently antagonized by intraplantar administration of the sulphonylureas tolbutamide (20, 40 and 160 microg) and glibenclamide (40, 80 and 160 microg), selective blockers of ATP-sensitive K(+) channels. 4. Charybdotoxin (2 microg paw(-1)), a selective blocker of high conductance Ca(2+)-activated K(+) channels, and apamin (10 microg paw(-1)), a selective blocker of low conductance Ca(2+)-activated K(+) channels, did not modify the peripheral antinociception induced by DbcGMP. 5. Tetraethylammonium (2 mg paw(-1)), 4-aminopyridine (200 microg paw(-1)) and cesium (800 paw(-1)), non-selective voltage-gated potassium channel blockers, also had no effect. 6. 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 Ca(2+)-activated K(+) channels and voltage-dependent K(+) channels appear not to be involved in the process.
Soares
A C
AC
Department of Pharmacology, Institute of Biological Sciences, UFMG, Av. Antônio Carlos, 6627, 31.270-100, Belo Horizonte, Brazil.
Duarte
I D
ID
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002586:Cesium / Q000494:pharmacology; D018999:Charybdotoxin / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology*; D015232:Dinoprostone / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005905:Glyburide / Q000494:pharmacology; D006614:Hindlimb / Q000187:drug effects / Q000473:pathology; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D010146:Pain / Q000517:prevention & control*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D000700:Analgesics; D015221:Potassium Channels; D018999:Charybdotoxin; D002586:Cesium; D001030:Apamin; D003995:Dibutyryl Cyclic GMP; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D015761:4-Aminopyridine; D015232:Dinoprostone; D005905:Glyburide