Differential regulation of adenylyl cyclase activity by mu and delta opioids in rat caudate putamen and nucleus accumbens

Sari E Izenwasser, B. Buzas, B. M. Cox

Research output: Contribution to journalArticle

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Abstract

The regulation of adenylyl cyclase by opioid receptor types was characterized in the rat nucleus accumbens, a brain region that is involved in the reinforcing effects of drugs of abuse, and in the caudate putamen, a region not implicated in drug reinforcement. Both mu and delta opioid ligands inhibited adenylyl cyclase activity in the nucleus accumbens and in the caudate putamen of rat, whereas the kappa agonist, U69,593 (5α,7α,8α)- (+)-N-methyl-N-[7-(1-(pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]- benzeneacetamide, was ineffective. The mu agonists, DAMGO and Tyr-D-Arg-Phe- Sar, were more potent inhibitors of the enzyme in caudate putamen than in nucleus accumbens. The delta-selective agonists, DSLET and [D-Ala2]- deltorphin II more potently inhibited adenylyl cyclase in nucleus accumbens than in caudate putamen. Inhibition of the enzyme by DAMGO and Tyr-D-Arg- Phe-Sar was antagonized by the mu-selective competitive antagonist, CTOP D- Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, and the noncompetitive mu antagonists, β-funaltrexamine and naloxonazine. Inhibition of adenylyl cyclase activity by the delta-selective ligands, DPDPE, DSLET and [D-Ala2]- deltorphin II was unaffected by these antagonists. Conversely, the delta- selective antagonists, ICI 174,864 N-allyl2-Tyr-(α-aminisobutyric acid)2- Phe-Leu-OH and naltrindole, blocked the effects of the delta but not the mu opioid ligands. Adenylyl cyclase activity in nucleus accumbens and in caudate putamen is subject to regulation by both mu and delta opioid receptors.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume267
Issue number1
StatePublished - Jan 1 1993
Externally publishedYes

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Caudate Nucleus
Putamen
Nucleus Accumbens
Adenylyl Cyclases
enkephalin, Ser(2), Leu(5), Thr(6)-
Opioid Analgesics
Ala(2)-MePhe(4)-Gly(5)-enkephalin
naltrindole
Ligands
phenylalanylleucine
D-Penicillamine (2,5)-Enkephalin
delta Opioid Receptor
mu Opioid Receptor
Street Drugs
Opioid Receptors
Enzyme Inhibitors
Acids
Brain
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

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title = "Differential regulation of adenylyl cyclase activity by mu and delta opioids in rat caudate putamen and nucleus accumbens",
abstract = "The regulation of adenylyl cyclase by opioid receptor types was characterized in the rat nucleus accumbens, a brain region that is involved in the reinforcing effects of drugs of abuse, and in the caudate putamen, a region not implicated in drug reinforcement. Both mu and delta opioid ligands inhibited adenylyl cyclase activity in the nucleus accumbens and in the caudate putamen of rat, whereas the kappa agonist, U69,593 (5α,7α,8α)- (+)-N-methyl-N-[7-(1-(pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]- benzeneacetamide, was ineffective. The mu agonists, DAMGO and Tyr-D-Arg-Phe- Sar, were more potent inhibitors of the enzyme in caudate putamen than in nucleus accumbens. The delta-selective agonists, DSLET and [D-Ala2]- deltorphin II more potently inhibited adenylyl cyclase in nucleus accumbens than in caudate putamen. Inhibition of the enzyme by DAMGO and Tyr-D-Arg- Phe-Sar was antagonized by the mu-selective competitive antagonist, CTOP D- Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, and the noncompetitive mu antagonists, β-funaltrexamine and naloxonazine. Inhibition of adenylyl cyclase activity by the delta-selective ligands, DPDPE, DSLET and [D-Ala2]- deltorphin II was unaffected by these antagonists. Conversely, the delta- selective antagonists, ICI 174,864 N-allyl2-Tyr-(α-aminisobutyric acid)2- Phe-Leu-OH and naltrindole, blocked the effects of the delta but not the mu opioid ligands. Adenylyl cyclase activity in nucleus accumbens and in caudate putamen is subject to regulation by both mu and delta opioid receptors.",
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N2 - The regulation of adenylyl cyclase by opioid receptor types was characterized in the rat nucleus accumbens, a brain region that is involved in the reinforcing effects of drugs of abuse, and in the caudate putamen, a region not implicated in drug reinforcement. Both mu and delta opioid ligands inhibited adenylyl cyclase activity in the nucleus accumbens and in the caudate putamen of rat, whereas the kappa agonist, U69,593 (5α,7α,8α)- (+)-N-methyl-N-[7-(1-(pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]- benzeneacetamide, was ineffective. The mu agonists, DAMGO and Tyr-D-Arg-Phe- Sar, were more potent inhibitors of the enzyme in caudate putamen than in nucleus accumbens. The delta-selective agonists, DSLET and [D-Ala2]- deltorphin II more potently inhibited adenylyl cyclase in nucleus accumbens than in caudate putamen. Inhibition of the enzyme by DAMGO and Tyr-D-Arg- Phe-Sar was antagonized by the mu-selective competitive antagonist, CTOP D- Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, and the noncompetitive mu antagonists, β-funaltrexamine and naloxonazine. Inhibition of adenylyl cyclase activity by the delta-selective ligands, DPDPE, DSLET and [D-Ala2]- deltorphin II was unaffected by these antagonists. Conversely, the delta- selective antagonists, ICI 174,864 N-allyl2-Tyr-(α-aminisobutyric acid)2- Phe-Leu-OH and naltrindole, blocked the effects of the delta but not the mu opioid ligands. Adenylyl cyclase activity in nucleus accumbens and in caudate putamen is subject to regulation by both mu and delta opioid receptors.

AB - The regulation of adenylyl cyclase by opioid receptor types was characterized in the rat nucleus accumbens, a brain region that is involved in the reinforcing effects of drugs of abuse, and in the caudate putamen, a region not implicated in drug reinforcement. Both mu and delta opioid ligands inhibited adenylyl cyclase activity in the nucleus accumbens and in the caudate putamen of rat, whereas the kappa agonist, U69,593 (5α,7α,8α)- (+)-N-methyl-N-[7-(1-(pyrrolidinyl)-1-oxaspiro[4,5]dec-8-yl]- benzeneacetamide, was ineffective. The mu agonists, DAMGO and Tyr-D-Arg-Phe- Sar, were more potent inhibitors of the enzyme in caudate putamen than in nucleus accumbens. The delta-selective agonists, DSLET and [D-Ala2]- deltorphin II more potently inhibited adenylyl cyclase in nucleus accumbens than in caudate putamen. Inhibition of the enzyme by DAMGO and Tyr-D-Arg- Phe-Sar was antagonized by the mu-selective competitive antagonist, CTOP D- Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2, and the noncompetitive mu antagonists, β-funaltrexamine and naloxonazine. Inhibition of adenylyl cyclase activity by the delta-selective ligands, DPDPE, DSLET and [D-Ala2]- deltorphin II was unaffected by these antagonists. Conversely, the delta- selective antagonists, ICI 174,864 N-allyl2-Tyr-(α-aminisobutyric acid)2- Phe-Leu-OH and naltrindole, blocked the effects of the delta but not the mu opioid ligands. Adenylyl cyclase activity in nucleus accumbens and in caudate putamen is subject to regulation by both mu and delta opioid receptors.

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