PubMed HealthSearch

PubMed · 8270180

Calcium channel antagonists and adenosine analogues decrease tolerance to opiate pentazocine and U 50488H.

Abstract

1. A single dose of pentazocine induces cross-tolerance the analgesic effects of the kappa agonist U 50488H. Tolerance is observed by means of the hot plate test or by the i.p. administration of acetic acid 6 or 24 hr after the priming dose, respectively. 2. The administration of the calcium channel antagonists, diltiazem, nifedipine or verapamil, reduces the degree of tolerance as assessed by the hot plate test or acetic acid administration. 3. The adenosine agonist N6-cyclopentyl adenosine significantly reduced the intensity of the process; in contrast, N6-cyclohexyladenosine antagonized the analgesic response to the opiate obscuring its influence on the process. 4. The results are discussed in relation to the interaction of calcium channel function in the analgesic response to the kappa opiates.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

E Contreras, L Quijada, A Germany, R Fleckenstein, A Hernández. 1993. Calcium channel antagonists and adenosine analogues decrease tolerance to opiate pentazocine and U 50488H.. https://doi.org/10.1016/0306-3623(93)90369-9

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Receptor-mediated activation of G-proteins by kappa opioid agonists in frog (Rana esculenta) brain membranes.

This study delineates the heterotrimeric guanine nucleotide binding regulatory protein (G-protein) types in frog (Rana esculenta) brain membranes and their activation by kappa opioid agonists. Ethylketocyclazocine (EKC), trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl)b enzeneacetamide (U-50,488) and bremazocine displayed dose-dependent, norbinaltorphimine-reversible stimulation of guanosine-5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding in crude membrane preparations. G-proteins were identified by Western-blotting using previously characterized specific antisera that were generated against mammalian G-protein alpha-subunits and beta-subunits. A photoreactive guanosine 5'-triphosphate (GTP) analog, [alpha-32P]GTP azidoanilide ([alpha-32P]AA-GTP) irreversibly labeled four proteins in the molecular weight range of 39-43 kDa. Ethylketocyclazocine and U-50,488 stimulated photolabelling of these proteins among which the 39 kDa band comigrated with the protein specifically labelled with the alpha(i2) antibody and the 40 kDa band was identified as alpha(o1). The other two bands were also stained with the alpha(common) antibody, but were not further identified. These results suggest that the endogenously expressed kappa opioid receptors that are present in frog brain interact with multiple G-proteins in situ. Furthermore, the structure of most G-proteins seems to be well preserved during phylogenesis.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal.

***micro***-, delta- and kappa-opioid receptors are widely expressed in the central nervous system where they mediate the strong analgesic and mood-altering actions of opioids, and modulate numerous endogenous functions. To investigate the contribution of the kappa-opioid receptor (KOR) to opioid function in vivo, we have generated KOR-deficient mice by gene targeting. We show that absence of KOR does not modify expression of the other components of the opioid system, and behavioural tests indicate that spontaneous activity is not altered in mutant mice. The analysis of responses to various nociceptive stimuli suggests that the KOR gene product is implicated in the perception of visceral chemical pain. We further demonstrate that KOR is critical to mediate the hypolocomotor, analgesic and aversive actions of the prototypic kappa-agonist U-50, 488H. Finally, our results indicate that this receptor does not contribute to morphine analgesia and reward, but participates in the expression of morphine abstinence. Together, our data demonstrate that the KOR-encoded receptor plays a modulatory role in specific aspects of opioid function.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh

Opioids disrupt Ca2+ homeostasis and induce carbonyl oxyradical production in mouse astrocytes in vitro: transient increases and adaptation to sustained exposure.

Pharmacologically distinct subpopulations of astroglia express mu, delta, and/or kappa opioid receptors. Activation of mu, delta, or kappa opioid receptors can destabilize intracellular calcium ([Ca2+]i) in astrocytes leading to cellular hypertrophy and reactive injury. To assess whether acute or sustained opioid exposure might adversely affect astroglial function by disrupting Ca2+ homeostasis or by producing reactive oxygen species, fura-2 and a novel fluorescent-tagged biotin-4-amidobenzoic hydrazide reagent, respectively, were used to detect [Ca2+]i and carbonyl oxidation products within individual murine astrocytes. Acute (3 h) exposure to mu; (H-Tyr-Pro-Phe (N-Me) -D-Pro-NH2; PLO17), delta ([D-Pen2, D-Pen5]-enkephalin), and kappa (trans-(+/-)-3, 4-dichloro-N-methyl-N-[2-(1-pyrr olidinyl) cyclohexyl] benzeneacetamide methanesulfonate; U50,488H) opioid agonists caused significant mean increases in [Ca2+]i and in the levels of oxidative products in astrocytes. In contrast, following 72 h of continuous opioid exposure, [Ca2+]i and carbonyl levels returned to normal, irrespective of opioid treatment. These preliminary findings indicate that opioids initially destabilize [Ca2+]i and increase reactive oxygen species in astrocytes; however, astrocytes later recover and adapt to sustained opioid exposure.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh