Protein associated with Myc (PAM) is involved in spinal nociceptive processing.
PAM (protein associated with Myc) is a potent inhibitor of adenylyl cyclases (ACs) which is primarily expressed in neurones. Here we describe that PAM is highly expressed in dorsal horn neurones and motoneuron of the spinal cord, as well as in neurones of dorsal root ganglia in adult rats. PAM mRNA expression is differentially regulated during development in both spinal cord and dorsal root ganglia of rats, being strongest during the major respective synaptogenic periods. In adult rats, PAM expression was up-regulated in the spinal cord after peripheral nociceptive stimulation using zymosan and formalin injection, suggesting a role for PAM in spinal nociceptive processing. Since PAM inhibited Galphas-stimulated AC activity in dorsal root ganglia as well as spinal cord lysates, we hypothesized that PAM may reduce spinal nociceptive processing by inhibition of cAMP-dependent signalling. Accordingly, intrathecal treatment with antisense but not sense oligonucleotides against PAM increased basal and Galphas-stimulated AC activity in the spinal cord and enhanced formalin-induced nociceptive behaviour in adult rats. Taken together our findings demonstrate that PAM is involved in spinal nociceptive processing.
Ehnert
Corina
C
pharmazentrum frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
Tegeder
Irmgard
I
Pierre
Sandra
S
Birod
Kerstin
K
Nguyen
Hong-Van
HV
Schmidtko
Achim
A
Geisslinger
Gerd
G
Scholich
Klaus
K
D048868:Adaptor Proteins, Signal Transducing; D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D005557:Formaldehyde; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D007796:Laminectomy / Q000379:methods; D008297:Male; D006899:Mixed Function Oxygenases; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013997:Time Factors; D044767:Ubiquitin-Protein Ligases; D015054:Zymosan
D048868:Adaptor Proteins, Signal Transducing; D000318:Adrenergic beta-Agonists; D000906:Antibodies; D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D016376:Oligonucleotides, Antisense; D011994:Recombinant Proteins; D005576:Colforsin; D005557:Formaldehyde; D015054:Zymosan; D006899:Mixed Function Oxygenases; C114022:MYCBP2 protein, human; D044767:Ubiquitin-Protein Ligases; D019205:GTP-Binding Protein alpha Subunits, Gs; D010751:Phosphopyruvate Hydratase; D000262:Adenylyl Cyclases; D007545:Isoproterenol