Inositol trisphosphate/Ca2+ as messengers of bradykinin B2 and muscarinic acetylcholine m1-m4 receptors in neuroblastoma-derived hybrid cells.
Neuroblastoma x glioma hybrid NG 108-15 and neuroblastoma x fibroblast hybrid NL308 cells possess endogenous bradykinin B2 receptors and m4 muscarinic acetylcholine receptors (mAChRs), which couple to phospholipase C and adenylate cyclase, respectively. Four genetic subtypes of mAChRs differed in their effects when stimulated in NG108-15 and NL308 cells overexpressing mAChRs. Broadly speaking, the principal effects fell into two categories: the odd-numbered receptors (m1 and m3) activated phospholipase C and increased inositol trisphosphate/Ca2+, as bradykinin did, whereas the even-numbered receptors (m2 and m4) inhibited adenylate cyclase via a pertussis toxin (PTx)-sensitive G-protein in NG108-15 cells. But all four types of NL308 cells overexpressing each m1, m2, m3 and m4 receptor activated phospholipase C, while keeping the PTx-sensitivity in m2/m4, but not in m1/m3 receptors. Coupling to ion channel effectors showed a comparable dichotomy in NG108-15 cells, while cross-activation occurred in NL308 cells.
Noda
M
M
Department of Biophysics, Kanazawa University School of Medicine, Japan.
Ishizaka
N
N
Yokoyama
S
S
Hoshi
N
N
Kimura
Y
Y
Hashii
M
M
Taketo
M
M
Egorova
A
A
Knijnik
R
R
Fukuda
K
K
Morikawa
H
H
Brown
D A
DA
Higashida
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D006822:Hybrid Cells; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction
D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D011976:Receptors, Muscarinic; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium