J. C. Lodder

Opposing roles for D-1 and D-2 dopamine receptors in regulating the excitability of growth hormone-producing cells in the snail Lymnaea stagnalis

Dopamine hyperpolarizes growth hormone-producing cells (GHC) in the CNS of Lymnaea stagnalis. This effect of dopamine was mimicked by the D-2 receptor agonist LY 141865 and antagonized by the D-2 receptor antagonists (-)-sulpiride and YM 09151-2. SKF 38393, a selective D-1 receptor agonist, increased the excitability of the GHC. This effect was mimicked by intracellular injection of cyclic AMP and antagonized by the D-1 receptor antagonist SCH 23390. Dopamine (in the presence of (-)-sulpiride) also increased the excitability of the GHC. It is concluded that both a D-1 and a D-2 receptor regulate the electrical activity of the GHC in the CNS of Lymnaea stagnalis.

Dopamine receptor stimulation induces a potassium dependent hyperpolarizing response in growth hormone producing neuroendocrine cells of the gastropod mollusc Lymnaea stagnalis

Of several putative transmitters used, dopamine was the only one which caused (at low concentrations) a hyperpolarizing response (H-response) in growth hormone producing cells (GHCs) of the freshwater snail Lymnaea stagnalis. Membrane resistance changes, and shifts in the reversal potential of this H-response in different K+-concentrations, indicate that the response is due to an increase in potassium conductance. The dopamine induced H-response is blocked by (-)-sulpiride, 4-aminopyridine, dibutyryl cAMP, 8CPT-cAMP, forskolin and IBMX. These data suggest that dopamine induces the H-response by stimulating a receptor resembling the mammalian D-2 receptor and that this effect of dopamine is mediated by a decrease in the formation of intracellular cAMP.

Further pharmacological characterization of a D-2-like dopamine receptor on growth hormone producign cells in Lymnaea stagnalis

A preliminary study has revealed that a mammalian D-2-like dopamine (DA) receptor mediates hyperpolarization of the neuroendocrine growth hormone-producing cells (GHCs) in the snail Lymnaea stagnalis. An extensive pharmacological characterization of this receptor was performed in the present study. Several mammalian D-2 receptor agonists (e.g. aminotetralins) and antagonists (e.g.(-)-sulpiride) showed agonistic and antagonistic effects, respectively. However, some selective D-2 receptor agonists (e.g. N 0437) and antagonists (e.g. domperidone) failed to show agonistic or antagonistic effects, respectively. It is concluded that the dopamine receptor mediating hyperpolarization of the GHCs displays, besides some similarities, several differences from the mammalian D-2 receptor.

A biphasic cholinergic input on the ovulation hormone producing caudo-dorsal cells of the freshwater snail Lymnaea stagnalis

Abstract 1. 1. Electrical stimulation of peripheral nerves elicits a biphasic response in the ovulation hormone producing Caudo-Dorsal Cells of Lymnaea stagnalis. 2. Acetylcholine was the only putative transmitter used, that was effective at low concentrations. 3. Two receptors mediating the response to ACh were characterized. 4. Drugs selectively acting upon ACh receptors also interfered with synaptic transmission activated by nerve stimulation. 5. It is concluded that the input of caudo-dorsal cells activated by nerve stimulation is cholinergic. .

Inhibitory modulation by FMRFamide of the voltage-gated sodium current in identified neurones in Lymnaea stagnalis.

1. The putative neurotransmitter FMRFa (Phe‐Met‐Arg‐Phe‐amide) caused an inhibitory modulation of the voltage‐gated sodium current (INa) in central neurones, the peptidergic caudo dorsal cells (CDCs) of the mollusc Lymnaea stagnalis. FMRFa reduced INa at all command potentials tested (ranging from ‐35 to +20 mV), but the amplitude of the effect of FMRFa was voltage dependent, inhibition being stronger at more negative potentials (50 +/‐ 5% reduction at half‐maximal INa activation versus 25 +/‐ 8% at the peak of the I‐V curve). 2. INa current traces were well fitted by a Hodgkin & Huxley based model, using m3 activation kinetics and two time constants for inactivation. 3. The steady‐state inactivation curve of INa was characterized by half‐maximal inactivation at ‐42.5 +/‐ 1.81 mV and a slope factor of 4.6 +/‐ 0.28 mV. The fastest time constant of inactivation ran from 100 +/‐ 5 to 0.8 +/‐ 0.32 ms and the slower time constant from 505 +/‐ 45 to 4.8 +/‐ 1.40 ms in the range ‐40 to ‐5 mV. 4. FMRFa had no significant effect on either component of inactivation, nor on the voltage dependence of steady‐state inactivation, nor on the maximal conductance. 5. FMRFa affected the activation of INa. The activation time constant was increased, ranging from 0.75 +/‐ 0.050 to 0.22 +/‐ 0.017 ms under control and from 0.91 +/‐ 0.043 to 0.31 +/‐ 0.038 ms with FMRFa in the voltage range ‐25 to +5 mV. The steady‐state activation curve was shifted to less negative potentials: half‐maximal activation occurred at ‐26.5 +/‐ 1.2 mV under control and at 23.6 +/‐ 1.4 mV with FMRFa; the slope factor (4.6 +/‐ 1.4 mV in control experiments) was not affected. The combination of slower activation kinetics and a shift in the voltage dependence of activation in the Hodgkin & Huxley based model, adequately explained the reduction of INa by FMRFa. 6. The physiological consequence is that the spiking threshold is increased, causing an arrest of on‐going firing activity and a decrease in excitability.

D-1 Dopamine Receptor Stimulation Increases, and D-2 Dopamine Receptor Stimulation Decreases, the Excitability of Growth Hormone Producing Cells in the Snail Lymnaea stagnalis

Dopamine (DA) induces biochemical and physiological effects in the mammalian central nervous system (CNS). The occurrence of a D-1 dopamine receptor (in the classification scheme of Kebabian and Calne, 1979) accounts for the ability of DA to enhance cyclic AMP formation. The occurrence of a D-2 dopamine receptor accounts for the ability of DA to inhibit cyclic AMP formation brought about by stimulation of a D-1 receptor (Stoof and Kebabian, 1981). This categorization of DA-receptors is currently accepted by most investigators.