Opposite effects of increased intracellular cyclic AMP on the heat and bradykinin responses of canine visceral polymodal receptors in vitro.
To clarify the validity of the long standing hypothesis that effects of E series prostaglandin (PG)S are mediated by cyclic AMP (cAMP), we studied the effects of increases in intracellular cAMP on the heat and bradykinin responses of testicular polymodal receptors. Polymodal receptor activities were recorded in vitro from testis-spermatic nerve preparations excised from dogs anesthetized with pentobarbital (30 mg/kg, i.v.). Increases in intracellular cAMP induced by either forskolin (5 or 10 microM), an adenylyl cyclase activator, or a mixture of dibutyryl cAMP (20-100 microM), a membrane permeable cAMP analog, and 3-isobutyl-1-methyl xanthine (20-100 microM), an inhibitor of the cAMP degrading enzyme, significantly augmented the response to heat (42-48 degrees C). In contrast, these substances failed to facilitate the response to bradykinin (0.1 or 1 microM) and instead suppressed it. Dideoxyforskolin (10 microM), an inactive analog of forskolin, had no effects on both the heat and bradykinin responses. These results demonstrate that an increase in intracellular cAMP induces opposite effects on the heat and bradykinin responses. Possible involvement of intracellular cAMP in the facilitatory effects of PGE2 on both responses was discussed in connection with the PGE receptor subtypes involved in the sensitization of the bradykinin and heat responses.
Mizumura
K
K
Department of Neural Regulation, Nagoya University, Japan.
Koda
H
H
Kumazawa
T
T
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004285:Dogs; D066298:In Vitro Techniques; D008297:Male; D009619:Nociceptors / Q000187:drug effects*; D013737:Testis / Q000187:drug effects*
D005576:Colforsin; D000242:Cyclic AMP; D015232:Dinoprostone; D001920:Bradykinin