Effects of receptor-selective neurokinin agonists and a neurokinin antagonist on the electrical activity of spinal cord neurones in culture.
1. Rat spinal cord neurones grown in tissue culture were used to examine the electrophysiological effects of the neurokin in (NK)-selective agonists (pGlu6, Pro9) substance P(6-11) (septide; NK1, 10(-6)M) and (pGlu5, MePhe8, MeGly9)SP(1-7) (DiMe-C7; NK3, 10(-6)M). In addition, the effect of the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP (10(-5)M) on the neurokinin-evoked responses was investigated. 2. Neurokinin-evoked responses consisted of an increase in neuronal activity with or without long-lasting (mean: 50s) depolarizations of the membrane potential of up to 25mV. The latter also occurred in the presence of tetrodotoxin (10(-7)M) (direct response). 3. In a number of spinal cord neurones (n = 17) only septide induced a membrane depolarization while DiMe-C7 elicited no response. On the other hand, in 2 neurones a response was exclusively evoked by DiMe-C7. 4. The neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP had no effect of its own but blocked the septide- and DiMe-C7-induced depolarizations. It had no effect on the glutamate (10(-5)M)-evoked depolarization. 5. It is concluded that by the use of neurokinin receptor-selective agonists, subpopulations of spinal cord neurones in primary dissociated cell culture can be differentiated which express the NK1 or the NK3 receptor. Cells expressing only the NK1 receptor outnumber those expressing only the NK3 receptor subtype. Both receptors can be blocked by the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP.
Wienrich
M
M
E. Merck, Biological Research, Darmstadt, F.R.G.
Reuss
K
K
Harting
J
J
D000818:Animals; D002478:Cells, Cultured; D004594:Electrophysiology; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments; D011247:Pregnancy; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D005971:Glutamates; D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D013373:Substance P; D013779:Tetrodotoxin; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; C054725:septide; D011761:Pyrrolidonecarboxylic Acid