Role of L-type Ca(2+) channels in pertussis toxin induced antagonism of U50,488H analgesia and hypothermia

Brain Res. 2002 Aug 16;946(2):191-7. doi: 10.1016/s0006-8993(02)02880-9.


Previous studies have shown that the kappa-opioid effects are sensitive to pertussis toxin (PTX) and affected by Ca(2+) fluxes. However, the possible involvement of Ca(2+) channels in PTX-induced inhibition of kappa-opioid effects has not been reported. The effect of intracerebroventricular (i.c.v.) treatment of pertussis toxin (1 microg/rat, PTX) or saline on the kappa-opioid agonist, U-50,488H (U5H) induced tail-flick analgesia and hypothermia in rats was determined. The effect of nimodipine (NIM), a dihydropyridine (DHP)-sensitive Ca(2+) channel blocker (CCB), on PTX-induced modulation of U5H effects was examined. The DHP ligand, [3H]PN200-110 binding was also determined in both PTX and saline treated rats to study the possible involvement of L-type Ca(2+) channels in PTX modulation of kappa-opioid agonist effects. The analgesia and change in colonic temperature were determined using tail-flick analgesiometer and telethermometer, respectively. U5H (40 mg/kg, i.p.) produced significant analgesic and hypothermic responses. PTX treatment significantly (P<0.01) antagonized the analgesic and hypothermic effects of U5H. Acute pretreatment of NIM (1 mg/kg, i.p.) 15 min prior significantly (P<0.01) reversed the PTX-induced antagonism of U5H effects. In the binding study, PTX treatment (72 h before) resulted in a significant (P<0.005) upregulation (+45% vs. saline control) of DHP binding (B(max)) with no change in affinity (K(d)). The results showed significant upregulation of DHP binding in accordance with PTX-induced antagonism of U5H effects and this blockade was reversed by NIM. Thus, present results suggest that U5H-induced analgesia and hypothermia may be mediated through PTX-sensitive transducer G-proteins (G(i/o)) coupled to L-type Ca(2+) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / antagonists & inhibitors*
  • Analgesics, Non-Narcotic / antagonists & inhibitors*
  • Animals
  • Body Temperature / drug effects
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / metabolism
  • Calcium Channels, L-Type / physiology*
  • In Vitro Techniques
  • Injections, Intraventricular
  • Isradipine / pharmacokinetics
  • Male
  • Membranes / metabolism
  • Nimodipine / pharmacology
  • Pain Measurement / drug effects
  • Pertussis Toxin / administration & dosage
  • Pertussis Toxin / pharmacokinetics
  • Pertussis Toxin / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / agonists


  • Analgesics, Non-Narcotic
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Receptors, Opioid, kappa
  • Nimodipine
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Pertussis Toxin
  • Isradipine