Elsevier

Neuroscience Research

Volume 43, Issue 2, June 2002, Pages 119-125
Neuroscience Research

Blockade of ionotropic receptor responses by progesterone in the ganglion cells of Aplysia

https://doi.org/10.1016/S0168-0102(02)00024-XGet rights and content

Abstract

To compare nongenomic effects of progesterone on various receptor responses of neurons, Aplysia ganglion cells were pretreated with 30 μM progesterone for 5 min and various receptor responses were tested using a conventional voltage-clamp method. Progesterone reduced nicotinic receptor-activated Na+-currents, nicotinic receptor-activated Cl-currents, γ-aminobutyric acid receptor-activated Cl-currents, and dopamine receptor-activated Na+-currents. These depressant effects are similar at two different agonist concentrations. On the other hand, progesterone affected neither muscarinic receptor-activated K+-currents nor dopamine receptor-activated K+-currents. The former four types of receptors are known to be ionotropic while the latter two types of receptors are known to be metabotropic. Therefore, progesterone selectively inhibited all the types of ionotropic receptor responses, presumably in a noncompetitive manner.

Introduction

The steroid hormone progesterone is known to act on nervous systems to produce various effects (Pfaff and McEwen, 1983). Progesterone interacts with its intracellular receptors and modifies cellular functions by altering transcription rates of some genes. In addition, progesterone produces more rapid alterations in neuronal excitability. For example, progesterone inhibited nicotinic receptor responses (Valera et al., 1992, Bullock et al., 1997, Blanton et al., 1999), serotonin type 3 (5-HT3) receptor responses (Wu et al., 2000), and glycine receptor responses (Wu et al., 1990), while it also facilitated γ-aminobutyric acid type A (GABAA) receptor responses (Wu et al., 1990). These effects of progesterone on transmitter–receptor responses occurred within minutes of application of progesterone without alterations in protein synthesis.

Progesterone or other steroids and also steroid metabolizing enzymes have been found in a mollusc Aplysia and other invertebrate species (Lehoux and Sandor, 1970, Lupo di Prisco et al., 1973, Lupo di Prisco and Dessi'Fulgheri, 1975). Works on the gonad organs of invertebrates (reviewed by Lehoux and Sandor, 1970) have suggested that in at least some species of invertebrates, steroids act as signaling molecules for physiological and developmental regulation. In addition, there are several studies reporting the regulatory effects of steroids on invertebrate nervous systems. For example, Concas et al. (1998) have shown that the metabolites of progesterone can modulate GABA receptor responses and behavior of Hydra vulgaris, one of the most primitive organisms with a nervous system. Kavaliers et al. (2000) have shown the antinociceptive effects of steroids in a mollusc, the land snail, Cepaea nemoralis. Hernández-Falcón et al. (1997) have shown the rapid nongenomic effects of steroids on photoreceptor excitability in the crayfish, Procambarus digueti. These findings have suggested that there may be an evolutionarily conserved modulation of neuronal receptor functions by steroids.

Aplysia ganglion cells have been used for the comparative studies of drug effects on different receptor responses of neurons, since various types of receptor responses of neurons are available for experiments in these cells. This paper is to compare the nongenomic effects of progesterone on various receptor responses in the ganglion cells of Aplysia. Examined responses in this paper include nicotinic type of Na+-current responses (Sato et al., 1968), another nicotinic type of Cl-current responses (Sato et al., 1968), GABA-induced Cl-current responses (Matsumoto, 1982), dopamine-induced Na+-current responses (Matsumoto et al., 1987), muscarinic type of K+-current responses (Sasaki and Sato, 1987), and dopamine-induced K+-current responses (Sasaki and Sato, 1987). The former four types of responses have been regarded to be mediated by ionotropic receptors, while the latter two types have been shown to be mediated by metabotropic receptors (Sasaki and Sato, 1987).

Section snippets

Preparation and perfusion

The abdominal ganglion of Aplysia kurodai was dissected out and fixed in a perfusing chamber. The connective tissue covering the ganglion cells was removed under binocular microscope, so that the cells were exposed continuously to perfusing solution. The ionic composition of the perfusing solution is Na+ 589, K+ 12, Cl 728, Ca2+ 14, Mg2+ 52, and dimethyl sulfoxide (DMSO) 4.2 mM. A Na+-free solution was made by replacing NaCl with equimolar tris(hydroxymethyl)aminomethane chloride, or

Results

To compare the nongenomic effects of progesterone on various receptor responses of neurons, we pretreated Aplysia ganglion cells with 30 μM progesterone for 5 min and tested various receptor responses using a conventional voltage-clamp method. Progesterone treatment itself occasionally caused a small shift in holding current and also a small change in slope conductance of the membrane (data not shown) but these effects were in most cases temporary and over before application of receptor

Discussion

It has been previously shown that through nongenomic mechanisms progesterone inhibited excitatory nicotinic receptor responses, excitatory 5-HT3 receptor responses, and inhibitory glycine receptor responses of neurons (Bullock et al., 1997, Wu et al., 2000, Wu et al., 1990). In this paper, we demonstrated that progesterone also inhibited the inhibitory nicotinic receptor response, the inhibitory GABA receptor response, and the excitatory dopamine receptor response of neurons within 5 min of

Acknowledgements

We are grateful to Emeritus Prof. Makoto Sato for his valuable suggestions and Ms Tada for her help. We thank Mr Ito and Mr and Mrs Ichikawa for constant supply of Aplysia. Part of this work was supported by the grants from the Ministry of Education, Science and Culture of Japan (Nos. 01770086 and 02770065) and the Grants-in-Aid for Advanced Medical Science Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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