title: Neurotensin and substance P: differential effects on plasma cholesterol levels in conscious ovariectomized rats.
abstract: Circulating plasma cholesterol levels were measured in conscious ovariectomized rats, bearing an indwelling silastic catheter in the external jugular vein, after intravenous (i.v.) pulse injection of 100 microliter 0.9% NaCl containing varying doses of neurotensin and/or substance P. Control injections of saline or decapeptide LH-RH or phosphate buffer did not modify plasma cholesterol levels. 10 or 20 micrograms doses of neurotensin produced a significant and dose-related increase in plasma cholesterol levels while similar doses of substance P had an opposite effect and induced a significant decline in plasma cholesterol levels in ovariectomized rats. 4-APP, a drug which selectively inhibits hepatic secretion of lipoproteins, significantly lowers plasma cholesterol to levels comparable to those produced by substance P. 4-APP and substance P induced hypocholesterolemia was readily reversed by a single dose of neurotensin. These findings indicate that neurotensin acts to increase circulating cholesterol levels and substance P antagonizes this hypercholesterolemic effect of neurotensin presumably by acting at some step in cholesterol transport. Reversal of the inhibitory effects of 4-APP and substance P on blood cholesterol by neurotensin may be through its action on hepatic secretion of lipoproteins, since 4-APP is known to lower circulating cholesterol by its specific action on hepatic secretion of lipoproteins.
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000315:Adrenalectomy; D000818:Animals; D002369:Castration; D002784:Cholesterol / Q000097:blood*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D051381:Rats; D013373:Substance P / Q000494:pharmacology*
chemical_list: C004420:4-aminopyrazolo(3,4-d)pyrimidine; D013373:Substance P; D007987:Gonadotropin-Releasing Hormone; D009496:Neurotensin; D002784:Cholesterol; D000225:Adenine