Pl. Wilkins et al., IMMORTALIZED SCHWANN-CELLS EXPRESS ENDOTHELIN RECEPTORS COUPLED TO ADENYLYL-CYCLASE AND PHOSPHOLIPASE-C, Neurochemical research, 22(4), 1997, pp. 409-418
Endothelins (ETs) are potent regulators of renal, cardiovascular and e
ndocrine functions and act as neurotransmitters in the CNS. Here we re
port that immortalized Schwann cells express receptors for ETs and cha
racterize some of the cellular events triggered by their activation. S
pecific binding of [I-125]-ET-1 to Schwann cell membranes was inhibite
d by ET-1 and the ETB-selective agonists ET-3, sarafotoxin 6c and [Ala
(1,3,11,15)]-ET-1 with IC50cor values ranging between 2 and 20 nM. No
competition was observed with the ETA receptor-selective antagonist BQ
123. Incubation of [H-3]-inositol pre-labeled Schwann cells with ET-I,
ET-3 or sarafotoxin 6c elicited a concentration-dependent increase in
the release of IP1 that reached a plateau at approximately 100 nM. Th
e efficacy of [Ala(1,3,11,15)]-ET-1 (a linear peptide analog of ET-1)
was half of that corresponding to ET-1. These stimulatory effects were
partially blocked by pre-incubation with pertussis toxin. When Schwan
n cells were incubated in the presence of 100 nM ET-1 or ET-3 there wa
s a significant inhibition of basal and isoproterenol-stimulated cAMP
levels. The inhibitory effects of sarafotoxin 6c and [Ala(1,3,11,15)]-
ET-1 On isoproterenol-stimulated cAMP levels were similar to that obse
rved with ET-1. Pre-incubation with pertussis toxin completely prevent
ed this effect. These observations indicate that immortalized Schwann
cells express receptors for ET peptides (predominantly ETB) coupled to
modulation of phospholipase C and adenylyl cyclase activities. The ac
tions of ETs on Schwann cells provide a novel example of the influence
of vascular factors on nerve function.