Participation of pertussis toxin-sensitive GTP-binding regulatory proteins in the suppression of baroreceptor reflex by neurotensin in the rat.
We evaluated the molecular mechanism that may underlie the suppressive effect of neurotensin (NT) on the baroreceptor reflex (BRR), using Sprague-Dawley rats that were anesthetized with sodium pentobarbital (50 mg/kg, i.p.). Intracerebroventricular (i.c.v.) application of NT (15 nmol) significantly inhibited the BRR response. Such an inhibition was appreciably antagonized by pretreating animals with i.c.v. injection of pertussis toxin (10 or 20 pmol), N-ethylmaleimide (1 or 2 nmol), forskolin (30 or 60 nmol) or phorbol 12-myristate 13-acetate (2 or 4 nmol), but not by cholera toxin (15 or 30 pmol). More specifically, pretreatments with bilateral microinjection into the nucleus tractus solitarius (NTS) of pertussis toxin (80 or 160 fmol), N-ethylmaleimide (80 pmol), forskolin (480 pmol) or phorbol 12-myristate 13-acetate (16 or 32 pmol) also blunted the NT-induced suppression of BRR, although cholera toxin (120 or 240 fmol), or 1,9-dideoxyforskolin (480 pmol) had no appreciable effect. These results suggest that a pertussis toxin-sensitive guanine nucleotide-binding regulatory protein(s), which is not likely to be Gs, possibly Gi or Gp, may be involved in the transmembrane signaling process that underlies the suppression of BRR response by NT at the NTS.
Fu
M J
MJ
Institute of Pharmacology, National Yang-Ming Medical College, Taipei, Taiwan, R.O.C.
Lin
K S
KS
Chan
J Y
JY
Chan
S H
SH
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D008297:Male; D009496:Neurotensin / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D037342:Pertussis Toxin; D011311:Pressoreceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D010566:Virulence Factors, Bordetella; D005576:Colforsin; D009496:Neurotensin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D005033:Ethylmaleimide; C047983:1,9-dideoxyforskolin