Role of Ca2+ channels on the hypothermic response produced by activation of kappa-opioid receptors.
The effect of nimodipine (NIM) and lercanidipine (LER) 1,4-dihydropyridine (DHP) calcium channel blockers (CCBs) on the hypothermic response of selective kappa-opioid receptor agonists U50,488H (U50), PD117,302 (PD) and U69,593 (U69) was determined in rats by recording colonic temperature using digital telethermometer. Intraperitoneal (i.p.) injections of U50 (7.5, 15, 22.5 and 40 mg/kg), PD (7.5, 15 and 22.5 mg/kg) and U69 (5 and 20 mg/kg) produced a dose-dependent hypothermic response. However, higher doses of U50 (60 and 80 mg/kg) produced hypothermia, which is less when compared to that produced by 22.5-mg/kg dose of U50. NIM (1 mg/kg i.p.; 15 min prior) and LER (0.3 mg/kg i.p.; 15 min prior) did not produce any change in basal colonic temperature. Treatment of NIM and LER potentiated the U50 (7.5, 15, 22.5 and 40 mg/kg)-induced hypothermic effect. NIM did not potentiate hypothermia produced by U50 (60 mg/kg). On the other hand, PD (7.5, 15 and 22.5 mg/kg)- and U69 (5 and 20 mg/kg)-induced hypothermia was unaffected by the pretreatment of either NIM or LER. This differential modulation of kappa-opioid agonist-induced hypothermia by CCBs suggest that there may be two mechanisms, Ca(2+)-sensitive and Ca(2+)-insensitive, involved in kappa-opioid agonist-induced hypothermic response.
Gullapalli
Srinivas
S
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, Phase-X, Sector 67, S.A.S. Nagar Mohali-160 062, Punjab, India.
Nemmani
Kumar V S
KV
Ramarao
Poduri
P
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D017473:Receptors, Opioid, kappa