RT Journal Article
SR Electronic
T1 Pharmacological discrimination between gamma-aminobutyric acid type B receptors regulating cholecystokinin and somatostatin release from rat neocortex synaptosomes.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 558
OP 562
VO 46
IS 3
A1 A Gemignani
A1 P Paudice
A1 G Bonanno
A1 M Raiteri
YR 1994
UL http://molpharm.aspetjournals.org/content/46/3/558.abstract
AB The gamma-aminobutyric acid (GABA)B receptors modulating the depolarization-evoked release of somatostatin (SRIF) or cholecystokinin (CCK) from superfused rat cerebrocortical synaptosomes have been characterized pharmacologically. GABA inhibited the 15 mM KCl-evoked overflow of both SRIF and CCK; the EC50 values were 1.3 microM and 1.4 microM, respectively. The GABAB receptor agonist (-)-baclofen also diminished the release of SRIF (EC50 = 1.9 microM) and CCK (EC50 = 2.6 microM). The novel compound CGP 47656, a highly selective GABAB receptor ligand, inhibited the release of SRIF, with its affinity and efficacy being similar to those of GABA or (-)-baclofen; however, the compound was unable to affect CCK release even when tested at 300 microM. The GABAB receptor antagonist phaclofen prevented, with identical affinities, the effects of (-)-baclofen on SRIF (pKb = 4.9) and CCK (pKb = 4.8) release. The same was true for CGP 35348, another GABAB receptor antagonist, which blocked (-)-baclofen with a pKb value of 6.1 at both the GABAB receptors regulating SRIF and CCK release. The effects of (-)-baclofen were also counteracted by the novel GABAB receptor antagonist CGP 52432. However, the affinity of the drug at the GABAB receptors modulating SRIF release (pKb = 6.2) was about 30-fold lower than that at the receptors regulating CCK release (pKb = 7.6). The data suggest that the GABAB receptors situated on nerve terminals releasing SRIF and CCK display pharmacological heterogeneity and may represent different subtypes of GABAB receptors.