Theophylline-induced nociceptive behavioral response in mice: possible indirect interaction with spinal N-methyl-D-aspartate receptors.
Intrathecal administration of an adenosine receptor antagonist, theophylline, elicited nociceptive behavior such as licking, biting and scratching in mice. This behavioral response was dose-dependently reduced by simultaneous injection of an adenosine receptor agonist, 5'-N6-ethylcarboxamidoadenosine, or a selective N-methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovalerate. This theophylline-induced behavior was not significantly reduced by the substance P (SP) analogue, the neurokinin receptor antagonist, [D-Arg1, D-Trp7.9, Leu11]SP (spantide). These results suggest the possibility that theophylline-induced nociceptive behavior may be mediated through interactions with both spinal adenosine- and NMDA receptors separately, or only through interaction(s) with adenosine receptors localized on the axon terminals of excitatory amino acid neurons. Present data have failed to reveal involvement of SP.
Nagaoka
H
H
Department of Pharmacy, Yamagata University Hospital, Japan.
Sakurada
S
S
Sakurada
T
T
Takeda
S
S
Nakagawa
Y
Y
Kisara
K
K
Arai
Y
Y
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D008297:Male; D051379:Mice; D010146:Pain; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000502:physiology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology*
D016194:Receptors, N-Methyl-D-Aspartate; D011983:Receptors, Purinergic; D013373:Substance P; D019830:Adenosine-5'-(N-ethylcarboxamide); D015763:2-Amino-5-phosphonovalerate; C042867:spantide; D013806:Theophylline; D000241:Adenosine