Design and synthesis of FMRF-amide-like peptides and their application to study of pain in spinal cord
Design and synthesis of FMRF-amide-like peptides and their application to study of pain in spinal cord
FMRFamide and ten FMRFamide-like peptides were manually synthesized on solid phase and their effects were tested on an isolated preparation of rat spinal cord. Dorsal root-ventral root monosynaptic reflexes (MSR) and dorsal horn field potentials (FP) were recorded and analyzed by computer. FLFQPQRFamide (NPFF) and AGEGLSSPFWSLAAPQRFamide (NPAF) both inhibited the fast component of the FP with similar potencies. FMRFamide also inhibited the FP but its potency was much lower. For MSR experiments, NPFF and NPAF potentiated the amplitude of the MSR while FMRFamide had no effect. PQRFamide, PRFRamide, FFRFamide, DPQRFamide, and Fmoc-FLFQPQRFamide were also examined on the MSR. PQRFamide and PFRFamide both potentiated the MSR whereas FFRFamide and DPQRFamide showed a slight MSR inhibition at high concentrations. The effect on the MSR was completely abolished when the N-terminal of NPFF was left protected with Fmoc-group. These results suggest that PFRFamide and PQRFamide may act as agonists of NPFF and NPAF, whereas the other peptides did not show such activity.
Two peptides recently cloned from human tissues, SQAFLFQPQRFamide (human NPFF) and AGEGLNSQFWSLAAPQRFamide (human NPAF) were also tested for their effects on MSR. Human NPFF did not induce any significant effect on MSR, but human NPAF produced a clear MSR amplitude potentiation in the similar manner to that induced by NPFF and NPAF. Since human NPFF is identical to NPFF except for three extra amino acids at the N-terminal, it may suggest that these extra amino acids (SQA) could hinder its binding or activating the receptors in the rat spinal cord. For human NPAF, its potency in potentiating MSR was not affected by a difference of two amino acids from NPAF within the peptides.
University of Southampton
1997
Huang, Eagle Yi-Kung
(1997)
Design and synthesis of FMRF-amide-like peptides and their application to study of pain in spinal cord.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
FMRFamide and ten FMRFamide-like peptides were manually synthesized on solid phase and their effects were tested on an isolated preparation of rat spinal cord. Dorsal root-ventral root monosynaptic reflexes (MSR) and dorsal horn field potentials (FP) were recorded and analyzed by computer. FLFQPQRFamide (NPFF) and AGEGLSSPFWSLAAPQRFamide (NPAF) both inhibited the fast component of the FP with similar potencies. FMRFamide also inhibited the FP but its potency was much lower. For MSR experiments, NPFF and NPAF potentiated the amplitude of the MSR while FMRFamide had no effect. PQRFamide, PRFRamide, FFRFamide, DPQRFamide, and Fmoc-FLFQPQRFamide were also examined on the MSR. PQRFamide and PFRFamide both potentiated the MSR whereas FFRFamide and DPQRFamide showed a slight MSR inhibition at high concentrations. The effect on the MSR was completely abolished when the N-terminal of NPFF was left protected with Fmoc-group. These results suggest that PFRFamide and PQRFamide may act as agonists of NPFF and NPAF, whereas the other peptides did not show such activity.
Two peptides recently cloned from human tissues, SQAFLFQPQRFamide (human NPFF) and AGEGLNSQFWSLAAPQRFamide (human NPAF) were also tested for their effects on MSR. Human NPFF did not induce any significant effect on MSR, but human NPAF produced a clear MSR amplitude potentiation in the similar manner to that induced by NPFF and NPAF. Since human NPFF is identical to NPFF except for three extra amino acids at the N-terminal, it may suggest that these extra amino acids (SQA) could hinder its binding or activating the receptors in the rat spinal cord. For human NPAF, its potency in potentiating MSR was not affected by a difference of two amino acids from NPAF within the peptides.
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Published date: 1997
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Local EPrints ID: 463083
URI: http://eprints.soton.ac.uk/id/eprint/463083
PURE UUID: b62f361f-2f99-4b62-b52d-3521a8bfc02e
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Date deposited: 04 Jul 2022 20:44
Last modified: 04 Jul 2022 20:44
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Author:
Eagle Yi-Kung Huang
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