Pharmacological characterization of tachykinin receptors controlling acetylcholine release from rat striatum: an in vivo microdialysis study.
The regulation of striatal cholinergic function by tachykinins was examined in urethane-anesthetized rats by using microdialysis. Substance P (0.01-1 microM), [Sar9, Met (O2)11]substance P (1-10 microM), septide (0.1-3 microM), neurokinin (NK) A (0.1-10 microM), and senktide (0.1-10 microM) produced concentration-dependent increases in striatal acetylcholine (ACh) release. Septide was the most potent agonist for inducing release of ACh, whereas the stimulating effect of senktide was less pronounced and more progressive in onset. The response to septide was prevented by intraperitoneal administration of the nonpeptide NK1 antagonist SR 140333 (1-3 mg/kg) but not by the nonpeptide NK2 receptor antagonist SR 48968, indicating that the effect was mediated specifically by NK1 receptors. ACh release caused by NKA was reduced by SR 48968 (1-3 mg/kg) and slightly affected by SR 140333, indicating a principal role for NK2 receptors in the peptide response. The similar efficacy of SR 140333 and SR 48968 in blocking substance P-induced ACh release suggested that the effect of this peptide involves the stimulation of both NK1 and NK2 receptors. Finally, our results indicate that the increase in striatal ACh release induced by the D1 agonist (+)-SKF-38393 (3 microM) may be mediated indirectly through local release of NKA or substance P acting at NK2 receptors.
Steinberg
R
R
Neuropsychiatry Research Department, Sanofi Recherche, Montpelllier, France.
Rodier
D
D
Souiclhac
J
J
Bougault
I
I
Emonds-Alt
X
X
Soubrié
P
P
Le Fur
G
G
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018039:Receptors, Tachykinin / Q000819:agonists / Q000502:physiology*
D001549:Benzamides; D018491:Dopamine Agonists; D010880:Piperidines; D011812:Quinuclidines; D018039:Receptors, Tachykinin; C085215:SR 140333; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C073839:SR 48968; D000109:Acetylcholine