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Neurokinin Receptors Could Be Differentiated by Their Capacity to Respond to the Transglutaminase‐Synthesized γ‐(Glutamyl 5 )Spermine Derivative of Substance P
Author(s) -
Esposito C.,
Mancuso F.,
Calignano A.,
Di Pierro P.,
Pucci P.,
Porta R.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65010420.x
Subject(s) - spermine , substance p , chemistry , spermidine , receptor , polyamine , neurokinin a , biochemistry , tissue transglutaminase , stereochemistry , neuropeptide , enzyme
Four different γ‐(glutamyl 5 )amine derivatives of substance P (SP) were synthesized in vitro in the presence of purified guinea pig liver transglutaminase and Ca 2+ . The 1,3‐diaminopropane, spermidine, spermine (Spm), and monodansylcadaverine adducts of the neuropeptide were purified by HPLC on a reversed‐phase column and characterized by fast atom bombardment mass spectrometry. The γ‐(glutamyl 5 )Spm derivative of SP (Spm‐SP) was found to be able, like the parent neuropeptide, to provoke rabbit aorta relaxation, to decrease rat arterial blood pressure, and to inhibit collagen‐induced platelet aggregation. Unlike SP, only a weak inflammatory response was observed when Spm‐SP was injected in the rat hind limb. All these effects were found to be prevented by N ω ‐nitro‐ l ‐arginine methyl ester, a well‐known nitric oxide synthesis inhibitor. In contrast, Spm‐SP was completely ineffective in contracting guinea pig ileal segments, thus confirming our preliminary observations indicating that Spm‐SP does not evoke SP‐like spasmogenic effects on isolated smooth muscle preparations. The specificity of the effects due to the selective introduction of a Spm moiety at the glutamine 5 level was demonstrated by the SP agonist pharmacological profile of the other γ‐(glutamyl 5 )amine derivatives tested. These results suggest that neurokinin receptors could be differentiated by their capacity to respond to Spm‐SP.