Differential expression of two isoforms of the neurokinin-1 (substance P) receptor in vivo.
Recent pharmacological and biochemical studies have suggested that there may be more than one molecular form of the neurokinin-1 receptor (NK-1), a long and short isoform differing in the length of their cytoplasmic carboxyl-terminal tails, but no definitive evidence of the existence of such NK-1 receptor isoforms in tissue has been presented. To examine whether these different isoforms are expressed in vivo we have compared the distribution of high affinity substance P (SP) binding sites (visualized by autoradiography with [125I]SP), with the distribution of the C-terminal epitope of the full length receptor (visualized with a specific antibody against the extreme C-terminal sequence). The former method labels both long and short forms of the NK-1 receptor, while the latter labels only the long form of the protein. In the rat there is a close correspondence of [125I]SP binding and NK-1 immunoreactivity in the striatum, suggesting that the long isoform predominates in this tissue. In the parotid and submaxillary gland, there are very high levels of [125I]SP binding but only low levels of NK-1 immunoreactivity, suggesting that expression of the short form predominates in these tissues. These results imply that different tissues express different ratios of the two isoforms of the NK-1 receptor. This differential expression provides the theoretical basis for tissue specific pharmacological targeting of NK-1 receptors.
Mantyh
P W
PW
Molecular Neurobiology Laboratory (151), Veterans Administration Medical Center, Minneapolis, MN 55417, USA. manty001@maroon.tc.umn.edu
Rogers
S D
SD
Ghilardi
J R
JR
Maggio
J E
JE
Mantyh
C R
CR
Vigna
S R
SR
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D003342:Corpus Striatum / Q000737:chemistry*; D007150:Immunohistochemistry; D008297:Male; D009928:Organ Specificity; D010306:Parotid Gland / Q000737:chemistry*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000032:analysis*; D013363:Submandibular Gland / Q000737:chemistry*
D018040:Receptors, Neurokinin-1