N-methyl-D,L-aspartate-induced growth hormone secretion in barrows: possible mechanisms of action.
Four experiments were conducted to determine mechanisms by which n-methyl-d,l-aspartate (NMA) increases serum concentrations of growth hormone (GH). Blood samples were collected from barrows every 15 min for 2 h (Exp. 1, 2, and 3) or 3 h (Exp. 4) immediately before and immediately after i.v. treatments. In Exp. 1, barrows (n = 4/treatment) received either .9% saline or 1.25, 2.5, or 5 mg of NMA/kg of BW. The change in circulating GH concentrations was greater (P < .05) for barrows receiving 2.5 mg (by 883%) or 5.0 mg of NMA/kg of BW (by 1,095%) than for those injected with saline. In Exp. 2, barrows (n = 4/treatment) received NMA (2.5 mg/kg of BW) or injections of 1.25 mg of the pure d or pure 1 isomers of NMA/kg of BW. Growth hormone concentrations increased by 177% (P < .025) after NMA treatment and by 245% (P < .01) after injection of the pure d isomer of NMA. The pure 1 isomer of NMA had no effect (P > .1) on GH concentrations. In Exp. 3, barrows received NMA (2.5 mg/kg of BW) 10 min after i.m. injection of saline (n = 7) or ketamine hydrochloride ( n = 8; 19.9 mg/kg of BW), an n-methyl-d-aspartate (NMDA) receptor antagonist. The NMA increased (P < .01) GH concentrations by 289% in saline-pretreated barrows but had no effect (P > .1) on barrows pretreated with ketamine hydrochloride. In Exp. 4, barrows (n = 4/treatment) received NMA 3 h after i.v. pretreatment with antisera to GH-releasing factor (GRF; 154 mL) or no pretreatment. Serum GH concentrations increased by 166% (P < .05) after injection of NMA in barrows receiving no pretreatment. The NMA had no effect (P > .1) on GH concentrations in barrows receiving antisera to GRF. Our results support the concept that NMDA stimulates GRF, and hence GH secretion, by activating an NMDA receptor.
Estienne
M J
MJ
Department of Agriculture, University of Maryland Eastern Shore, Princess Anne 21853, USA.
Harter-Dennis
J M
JM
Barb
C R
CR
Hartsock
T G
TG
Campbell
R M
RM
Armstrong
J D
JD
D000818:Animals; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000276:immunology / Q000502:physiology; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D007275:Injections, Intravenous / Q000662:veterinary; D007536:Isomerism; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013552:Swine / Q000097:blood* / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D007106:Immune Sera; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D007649:Ketamine; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone