Possible involvement of gamma-aminobutyric acid in growth hormone release induced by a Met5-enkephalin analog in conscious rats.

The interaction between opioid peptides and gamma-aminobutyric acid (GABA) in regulating GH secretion was studied in unanesthetized male rats with chronically implanted intraatrial catheters. GH secretion was pulsatile with GH bursts (mean +/- SE, 259.1 +/- 70.3 ng/ml) occurring at regular intervals (mean +/- SE, 3.6 +/- 0.2 h) in control rats. When a potent met5-enkephalin analog, FK 33-824 ([D-Ala,MePhe4,Met(O)-ol]enkephalin; 10 micrograms/100 g BW), was injected iv in the interval between two anticipated spontaneous GH bursts, plasma GH abruptly increased to a peak value of 716.0 +/- 144.9 ng/ml 20 min after the injection, and the following spontaneous GH burst appeared at longer intervals than expected (5.0 +/- 0.4 h, P less than 0.025 vs. control). The plasma GH increase induced by FK 33-824 was blunted by a specific opiate antagonist, naloxone (125 micrograms/100 g BW, iv), and the following spontaneous GH bursts occurred at the same time as in controls. The plasma GH response to FK 33-824 was significantly inhibited by two GABA antagonists, picrotoxin (0.3 mg/100 g BW, iv) and bicuculline (60 micrograms/100 g BW, iv), with peak GH values of 24.6 +/- 6.4 and 136.4 +/- 35.2 ng/ml, respectively (P less than 0.01 vs. FK 33-824 alone). The following natural GH bursts were also inhibited by these GABA antagonists (50.1 +/- 21.3 and 35.3 +/- 9.6 ng/ml; P less than 0.01 vs. control). These findings suggest the possible involvement of GABA in GH release induced by opioid peptides in the rat.