Formation of releasable gamma-aminobutyrate from putrescine by rat adrenal slices in vitro.
Rat adrenal gland slices, when incubated in vitro with [1,4-14C]putrescine, accumulate the radioactive diamine and convert it, in part, to a compound indistinguishable (in four separative systems) from [14C]gamma-aminobutyrate (GABA). Adrenal glands taken from animals that had undergone adrenal enucleation 28 days previously, so that the cortex of the tissue had regenerated, likewise formed [14C]GABA from [1,4-14C]putrescine. Putrescine-derived GABA was released from adrenal slices in vitro by 48 mmol K+/l, the release being dependent upon the presence of Ca2+ in the incubation medium. ACTH(1-24) and 8-bromocyclic AMP both provoked a dose-related release of putrescine-derived GABA, although the dose-response curve for the latter differed somewhat from that for the release of corticosterone by this secretogogue. The enzyme believed to be responsible for the first step in the metabolic transformation of putrescine into GABA, diamine oxidase (DAO), is present in extracts of adrenal tissue and its catalytic activity underwent a transient increase followed by a fall below resting levels upon stimulation of adrenal slices with ACTH(1-24). The conclusion that this enzyme initiates the formation of GABA by this pathway is indicated by the observation that adrenal slices pretreated with the DAO inhibitor, aminoguanidine, released significantly less [1,4-14C]putrescine-derived GABA in response to 48 mmol K+/l than did control tissues. The functional significance of these findings remains to be established.
Oon
B B
BB
Division of Biochemistry, United Medical School, Guy's Hospital, London.
Scraggs
P R
PR
Gillham
B
B
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000311:Adrenal Glands / Q000378:metabolism*; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003366:Cosyntropin / Q000494:pharmacology; D046508:Culture Techniques; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000494:pharmacology; D011700:Putrescine / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D006146:Guanidines; D003366:Cosyntropin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D005680:gamma-Aminobutyric Acid; D006631:Amine Oxidase (Copper-Containing); D011188:Potassium; C004479:pimagedine; D002118:Calcium; D011700:Putrescine