gamma-Aminobutyric acid (GABA) stimulates somatostatin release following activation of a GABA uptake carrier located on somatostatin nerve endings of rat cerebral cortex.
The effect of gamma-aminobutyric acid (GABA) on the release of somatostatin-like immunoreactivity (SRIF-LI) was studied in synaptosomes prepared from rat cerebral cortex and exposed in superfusion to the amino acid. GABA (1-300 microM) increased the spontaneous outflow of SRIF-LI in a concentration-dependent manner. The effect of GABA was not prevented by the GABAA receptor antagonists bicuculline or picrotoxin. The GABAA receptor agonist muscimol (10-100 microM) did not affect SRIF-LI release. Similarly ineffective was the GABAB receptor agonist (-)-baclofen (100 microM). The GABA-induced SRIF-LI release was counteracted by the GABA uptake inhibitors N-(4,4-diphenyl-3-butenyl)-nipecotic acid (SK&F 89976A) and nipecotic acid. When used as a GABA carrier substrate, nipecotic acid mimicked GABA and increased SRIF-LI release; its effect was antagonized by SK&F 89976A. The mechanism involved appears to be selective for GABA inasmuch as neutral amino acids such as leucine, alpha-aminobutyric acid or valine, tested at 100 microM, had little or no effect on the release of SRIF-LI. Neither GABA (100 microM) nor nipecotic acid (300 microM) enhanced the release of cholecystokinin-like immunoreactivity. The GABA-evoked somatostatin release was calcium-dependent and tetrodotoxin-insensitive. It is concluded that a carrier for the uptake of GABA exists on somatostatin-releasing terminals of rat cerebral cortex and that GABA uptake may regulate somatostatin release. This conclusion would be compatible with the reported coexistence of GABA and somatostatin in cerebrocortical neurons.
Raiteri
M
M
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Bonanno
G
G
Fedele
E
E
Fontana
G
G
Gemignani
A
A
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D009557:Nipecotic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013004:Somatostatin / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000596:Amino Acids; D000927:Anticonvulsants; D001640:Bicuculline; D003470:Culture Media; D009557:Nipecotic Acids; D010852:Picrotoxin; D013004:Somatostatin; D005680:gamma-Aminobutyric Acid; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid