Bicuculline-insensitive gaba receptors on peripheral autonomic nerve terminals

Bowery, Norman G.; Doble, Adam; Hill, David R.; Hudson, Alan L.; Shaw, John S.; Turnbull, M J; Warrington, Ruth

doi:10.1016/0014-2999(81)90386-1

Cited by 370 publications

(119 citation statements)

References 33 publications

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“…On day 7, the binding of (-)-[3H]baclofen by larvae was measured as described in the legend to Fig. 2. central nervous system, including the GABAA receptor [where muscimol is the most potent (27,28)] and the GABAB receptor [where (-)-baclofen and GABA are approximately equipotent (29)(30)(31)]. In experiments similar to those shown, we have found that the receptors characterized in these studies are stereochemically specific; (+)-baclofen is several orders of magnitude less effective than the (-)-enantiomer, in competition for the labeled receptors and in the induction of metamorphosis.…”

mentioning

confidence: 99%

Availability of chemosensory receptors is down-regulated by habituation of larvae to a morphogenetic signal.

Trapido-Rosenthal¹,

Morse²

1986

Proc. Natl. Acad. Sci. U.S.A.

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Larvae of the gastropod mollusc Haliotis rufescens are induced to settle from the plankton and metamorphose in response to exogenous y-aminobutyric acid (GABA) and a number of GABA-mimetic compounds, including a GABA-mimetic inducer uniquely associated with the surfaces of the naturally recruiting algae. Previous evidence has shown that recognition of these inducers is mediated by specialized chemosensory receptors on the larval epithelium and that transduction of the morphogenetic signal then is mediated by cAMP and excitatory depolarization. We demonstrate here the specific and saturable labeling of a population of larval receptors with the GABA analog f-(p-chlorophenyl)-[3H]GABA ([3H]baclofen); identification of these labeled receptors with those controlling metamorphosis is suggested by four independent criteria: (i) the effectiveness of GABA and its close structural analogs to induce metamorphosis is closely correlated with the effectiveness ofthese compounds to compete for binding to this receptor; (ii) the natural inducer purified from the recruiting algae competes for binding to this receptor; (iii) (-)-[3H]baclofen specifically bound to the receptors is shed from the larvae after %20 hr, at the time corresponding to the metamorphic abscission and shedding of sensory cilia and other structures from the larvae; and (iv) the availability of the receptors for labeling and the ability of the larvae to respond to GABA and GABA analogs can be down-regulated in parallel by habituation of the larvae early in their development. These down-regulated larvae are fully capable of settlement and metamorphosis in response to agents that elevate intracellular cAMP or depolarize the chemosensory membrane, confirming that down-regulation is confined to the receptors, with no effect on the postreceptor pathway. The results reported here thus suggest that the sensitivity of marine invertebrate larvae to morphogenetic stimuli from the environment can be downregulated by reduction in the number of chemosensory receptors available for interaction with the molecules that induce settlement and metamorphosis. In this respect, chemosensory receptors for environmental and morphogenetic signals are demonstrated biochemically to respond to habituation in a similar manner to neuronal and hormonal receptors.Larvae of many benthic marine invertebrate animals, after dispersal in the plankton, are induced to settle and metamorphose only upon recognition of specific substrata (1-8). Larvae (0.2 mm) of the Pacific red abalone, Haliotis rufescens, a gastropod mollusc, are induced to settle, attach to substrata, and metamorphose by chemosensory recognition of y-aminobutyric acid (GABA)-mimetic molecules that are uniquely associated with the surfaces of crustose red algae (9, 10). These purified natural inducers alone, GABA, and a number of GABA analogs are sufficient to induce this genetically programed behavioral and morphogenetic sequence (11-14); in the absence of such inducers, the larvae do not settle or metamorphose (11)(12)(13)...

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mentioning

confidence: 99%

Availability of chemosensory receptors is down-regulated by habituation of larvae to a morphogenetic signal.

Trapido-Rosenthal¹,

Morse²

1986

Proc. Natl. Acad. Sci. U.S.A.

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“…GABA has been shown previously to affect indirectly cardiac function at the peripheral level by inhibiting, through prejunctional GABAB receptors, noradrenaline release from sympathetic nerves (Bowery et al, 1981). Neely et al (1983) showed that, following selective perfusion of the sinus node artery, GABA had no direct effects on heart rate but attenuated, in a picrotoxin-sensitive manner, the bradycardia resulting from vagal stimulation.…”

Section: Discussionmentioning

confidence: 98%

“…The actions of GABA are in the mammalian peripheral nervous system (see mediated, depending on either the species or the Jessen et al, 1979;Giotti et al, 1983; preparations, or both, used, by at least two distinct Bowery, 1986). From these experiments evidence has types of GABA receptors termed GABAA and accumulated which suggests that GABA has a wide-GABAB according to the classification proposed by spread neuromodulatory action on autonomic Bowery et al (1981).…”

Section: Introductionmentioning

confidence: 99%

GABA_A receptor‐mediated positive inotropism in guinea‐pig isolated left atria: evidence for the involvement of capsaicin‐sensitive nerves

Maggi

Giuliani

Manzini

et al. 1989

British J Pharmacology

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1 Isolated left atria from reserpine-pretreated guinea-pigs, electrically driven (3 Hz) in the presence of atropine (1.uM), phentolamine (0.3 pM) and propranolol (1I M), responded to a train of stimuli (10 Hz for 2.5 s) with a delayed neurogenic positive inotropic response which was insensitive to hexamethonium (10pM) but abolished by either tetrodotoxin (1 pM), w..conotoxin (0.1 pM), in vitro capsaicin desensitization or desensitization to calcitonin gene-related peptide (CGRP). 2 In these experimental conditions, y-aminobutyric acid (GABA) produced a concentration-related (10.pM-1 mM) positive inotropic response similar to that produced by electrical field stimulation.The effect of GABA was competitively antagonized by bicuculline methiodide (10pM), a GABAA receptor antagonist. 3 The selective GABAA receptor agonists, muscimol and homotaurine mimicked the positive inotropic effect of GABA while baclofen, the selective GABAB receptor agonist, did not. 4 The action of GABA (1 mM) was abolished by either tetrodotoxin (1 pM), c-conotoxin (0.1 pM), in vitro capsaicin desensitization or desensitization to CGRP, while it was unaffected by hexamethonium. In contrast, the inotropic response to CGRP was unaffected by tetrodotoxin, cwconotoxin, bicuculline methiodide, hexamethonium or in vitro capsaicin desensitization, but was abolished by CGRP desensitization. 5 In the spontaneously beating guinea-pig right atrium, GABA (1 pM) produced a small and transient positive chronotropic effect that was no longer observed after in vitro desensitization with capsaicin (1 PM). 6 In the guinea-pig isolated perfused heart from reserpine-pretreated animals (with atropine, phentolamine and propranolol in the perfusion medium), GABA (1 pM) produced a transient tachycardia and a small increase in coronary flow. Both capsaicin (1 pM) and CGRP (1 pM) produced marked tachycardias and increases in coronary flow. After exposure to capsaicin (1 pM), no effect of GABA could be detected. 7 We conclude that, in the guinea-pig heart, GABAA receptors, presumably located on the preterminal region of capsaicin-sensitive sensory nerves, initiate a conducted impulse (since it is tetrodotoxin-sensitive) which leads to transmitter release (endogenous CGRP-like material) by activation of co-conotoxin-sensitive, voltage-sensitive calcium channels and a functional response.

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“…to reduce transmitter release at nerve terminals are mediated by different receptors since only the former changes can be inhibited by bicuculline (Brown & Higgins, 1979;Bowery, Hill, Hudson, Doble, Middlemiss & Tumbull, 1980;Bowery et al, 1981;Kato & Kuba, 1980). The former site has been referred to as GABAA and the latter as GABAB .…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Action of Γ‐aminobutyric Acid on the Excitatory but Not Inhibitory Innervation of the Rat Anococcygeus Muscle

Hughes

Morgan

Stone

1982

British J Pharmacology

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1 The effects of y-aminobutyric acid (GABA), ethylenediamine, 3-aminopropane sulphonic acid and (±)-baclofen have been examined on the responses to stimulation of the adrenergic excitatory and non-adrenergic non-cholinergic inhibitory innervation of the rat anococcygeus muscle in vitro. 2 GABA produced a dose-related depression of the contractile responses to field stimulation. Ethylenediamine and baclofen also depressed the contractile responses, though they were less potent than GABA. 3-Aminopropane sulphonic acid was almost inactive. The inhibitory action of GABA was not modified by phentolamine, propranolol or bicuculline methylbromide. 3 GABA did not affect the contractile responses of the anococcygeus muscle to noradrenaline, phenylephrine or carbachol in untreated muscles or those treated with 6-hydroxydopamine in vitro. 4 In preparations in which tone was raised by continuous perfusion with carbachol in the presence of phentolamine, field stimulation relaxed the muscle. GABA had no effect on this inhibitory response, and did not itself produce any relaxation. 5 It is concluded that GABA exerts a presynaptic inhibitory action on the excitatory adrenergic but not on the inhibitory innervation of the anococcygeus muscle, and that the GABA receptor involved exhibits properties of the previously described GABAB site.

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Bicuculline-insensitive gaba receptors on peripheral autonomic nerve terminals

Cited by 370 publications

References 33 publications

Availability of chemosensory receptors is down-regulated by habituation of larvae to a morphogenetic signal.

Availability of chemosensory receptors is down-regulated by habituation of larvae to a morphogenetic signal.

GABA_A receptor‐mediated positive inotropism in guinea‐pig isolated left atria: evidence for the involvement of capsaicin‐sensitive nerves

Inhibitory Action of Γ‐aminobutyric Acid on the Excitatory but Not Inhibitory Innervation of the Rat Anococcygeus Muscle

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Bicuculline-insensitive gaba receptors on peripheral autonomic nerve terminals

Cited by 370 publications

References 33 publications

Availability of chemosensory receptors is down-regulated by habituation of larvae to a morphogenetic signal.

Availability of chemosensory receptors is down-regulated by habituation of larvae to a morphogenetic signal.

GABAA receptor‐mediated positive inotropism in guinea‐pig isolated left atria: evidence for the involvement of capsaicin‐sensitive nerves

Inhibitory Action of Γ‐aminobutyric Acid on the Excitatory but Not Inhibitory Innervation of the Rat Anococcygeus Muscle

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GABA_A receptor‐mediated positive inotropism in guinea‐pig isolated left atria: evidence for the involvement of capsaicin‐sensitive nerves