Epinephrine mediates the growth hormone-releasing effect of galanin in infant rats.
The mechanism underlying the GH-releasing effect of galanin (GAL), a novel 29-amino acid peptide, was investigated in the neonatal rat. The effect of galanin was compared to that of clonidine (CLO), a drug known to release GH via endogenous GHRF. GAL administration (5-25 micrograms/kg BW, sc) induced in 10-day-old pups a clear-cut and dose-related rise in plasma GH 15 min postinjection. CLO (50-450 micrograms/kg BW, sc) induced a marked rise in plasma GH, but no dose-related effect was evident. Inhibition of hypothalamic norepinephrine and epinephrine biosynthesis by DU-18288 (6 mg/kg BW, ip) or selective inhibition of epinephrine biosynthesis by SKF-64139 (50 mg/kg BW, ip) completely abolished the GH-releasing effect of GAL (25 micrograms/kg, sc), but left unaltered the GH rise induced by CLO (150 micrograms/kg, sc). Passive immunization with an anti-GHRF serum decreased basal GH levels and prevented the GH-releasing effect of either GAL or CLO, whereas in pups pretreated with an antisomatostatin serum, CLO, but not GAL, increased the already elevated plasma GH titers. In all these data indicate that in the infant rat 1) GAL is a potent GH secretagogue; 2) the action of GAL is not exerted directly on GHRF- or somatostatin-secreting structures, but requires the intervention of catecholaminergic neurons; 3) the GH-releasing effect of GAL is ultimately exerted via GHRF release, although a mechanism operating to inhibit hypothalamic somatostatin release cannot be ruled out; and 4) differently from GAL, CLO releases GH via postsynaptic stimulation of GHRF-secreting neurons.
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors; D004837:Epinephrine / Q000502:physiology*; D005260:Female; D019004:Galanin; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000276:immunology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007116:Immunization, Passive; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D044005:Tetrahydroisoquinolines; D014230:Triazoles / Q000494:pharmacology
D007546:Isoquinolines; D010455:Peptides; D044005:Tetrahydroisoquinolines; D014230:Triazoles; C040439:N,N-dimethyl-N'-1H-1,2,4-triazol-3-yl-thiourea; D019004:Galanin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; C012153:7,8-dichloro-1,2,3,4-tetrahydroisoquinoline; D004299:Dopamine beta-Hydroxylase; D010625:Phenylethanolamine N-Methyltransferase; D003000:Clonidine; D009638:Norepinephrine; D004837:Epinephrine