Dual population of GABA_A and GABA_B receptors in rat pars intermedia demonstrated by release of αMSH caused by barium ions

Abstract

1 We have studied the effects of selective GABAA and GABAB agonists on x-melanophore stimulating hormone (aMSH) release from intact rat neurointermediate lobes (NIL) in vitro. Agonist effects were tested against either basal ocMSH output or BaCl2 (5 mM)-evoked release. 2 GABA (501M) produced a biphasic effect on basal release, with an enhancement followed by inhibition of release. The enhancement but not the inhibition was blocked by bicuculline methiodide (100 MLM). 3 Baclofen (10jM), a specific GABAB agonist, reduced the basal and Ba2+-evoked hormonal release in a stereospecific manner. (-)-Baclofen (5 jM) was active whereas the (+)-isomer was inactive at the same concentration. 4 Isoguvacine (501M) a specific GABAA agonist, potentiated the Ba2+-evoked release of axMSH. GABA (50I1M) mimicked this effect, and its action was antagonized by bicuculline methiodide (200 11M).5 The results suggest that both GABAA and GABAB receptors are present on the endocrine cells of the intermediate lobe.

A patch clamp study of γ‐aminobutryic acid (GABA)‐induced macroscopic currents in rat melanotrophs in cell culture

“…The results of binding assays have indicated that GABAB type receptors are present on cultured porcine melanotrophs and in this same preparation baclofen inhibits the spontaneous or barium-induced release of a-MSH (Demeneix et al, 1984;. Indirect evidence for a similar relationship between GABAB receptors and hormone release in rat melanotrophs is provided by the observations of Taraskevich & Douglas (1985), that the selective GABAA agonist isoguvacine reproduces the stimulatory but not the inhibitory effect of GABA itself.…”

“…From the observation that the barium-stimulated release of x-MSH is selectively enhanced by isoguvacine, a GABAA receptor agonist, and reduced by baclofen, a GABAI receptor agonist (Demeneix et al, 1984; it has been inferred that the stimulatory and inhibitory actions of GABA itself reflect the consequences of GABAA and GABAB receptor occupation, respectively.…”

Effectiveness of GABAB antagonists in inhibiting baclofen‐induced reductions in cytosolic free Ca concentration in isolated melanotrophs of rat

“…The physiological function of this GABA is not clear (see Kongsamut et al, 1991) but in vitro experiments have shown that application of GABA to melanotrophs directly affects electrical activity (Taraskevich & Douglas, 1982;, output of hormones Demeneix et al, 1984) and the concentration of cytosolic free Ca ([Ca2+]i) (Nemeth et al, 1988;. Moreover, release of endogeneous GABA has been demonstrated, albeit indirectly, by a 'postsynaptic' effect recorded in melanotrophs upon stimulation of the pituitary stalk (MacVicar & Pittman, 1986;Williams et al, 1989).…”

Why Are Several Inhibitory Transmitters Present in the Innervation of Pituitary Melanotrophs?

“…A remarkable feature of this innervation, ob served in various species, is that it contains nerve fibers of differ ent sorts containing several different transmitters that can in hibit meianotroph secretion. Why several inhibitory transmit ters should be present is unknown and it is with this enigma that we are here concerned.Within the innervation to the melanotrophs, dopamine must be regarded as the classic neurotransmitter and inhibitor of me ianotroph secretion [1,2], In addition, y-aminobutyric acid (GABA) is present [3][4][5][6] and, like dopamine, has been shown to act directly on melanotrophs to reduce secretion [7][8][9], Pep tidergic fibers have also been detected [10, 11[; and, in anuran …”