George B. Stefano

Neuropeptides and immunoregulation

Neuropeptides and Autoregulatory Immune Processes.- Role of Neuropeptides in the Bidirectional Communication Between the Immune and Neuroendocrine Systems.- Corticotropin and Immunoregulation.- ?-Melanotropin and its Role in Regulating the Inflammatory Response.- Immunoregulation by Neuropeptides Other than Corticotropin and Melanotropin.- Enkephalins as Regulators of Inflammatory Immune Reactions.- Interactions of Neuropeptides and Cytokines.- Stress and Immunity.- Pharmacological and Binding Evidence for Opioid Receptors on Vertebrate and Invertebrate Blood Cells.- Degradation of Neuropeptide Signal Molecules in Immunocytes of Vertebrates and Invertebrates.

Opposite effects of interleukin-2 and interleukin-4 on GABA-induced inward currents of dialysed Lymnaea neurons

1. The effects of interleukin-2 (rhIL-2) and interleukin-4 (rhIL-4) were investigated on gamma-aminobutyric acid (GABA)-induced inward currents on isolated, identified neurons of Lymnaea stagnalis L. (Mollusca, Gastropoda) by using a concentration clamp technique. 2. It was shown that the interleukins modified the GABA-induced inward current in an opposite direction: rhIL-2 (2-100 U/ml) decreased the peak value of IGABA in a dose-dependent manner, whereas rhIL-4 (0.2-100 U/ml), on the contrary, potentiated it. Both types of modulation were partially or fully reversible. 3. The reversal potential of IGABA was not shifted by these cytokines. 4. The time-to-peak value and inactivation time constant of the gamma-aminobutyric acid (GABA)-induced current was decreased by rhIL-4. The modulatory effect of rhIL-4 was eliminated after conjugation of this cytokine with its antibody. 5. It appears that cytokines could play a role in regulating the neural excitability through GABA-erg mechanisms.

Met-enkephalin and morphiceptin modulate a GABA-induced inward current in the CNS of Lymnaea stagnalis L

1. The interaction between GABA and opioid peptides (met-enkephalin and morphiceptin) was studied on the identified, isolated and internally perfused neurons of Lymnaea stagnalis L. (Gastropoda, Basommatophora). 2. GABA (10(-7)-10(-5)M) activated a Cl-dependent inward current with about -20 mV equilibrium potential. Slow and fast GABA-induced inward currents were recorded with different kinetic parameters in distinct identified neurons. 3. Both types of GABA-induced inward currents were reduced or blocked by met-enkephalin (10(-7)-10(-5)M) and morphiceptin (10(-7)-10(-5)M) in a dose-dependent manner. GABA-activated fast inward current was modulated in a biphasic way in some neurons. Opioid reduction of the GABA-activated slow inward current was reversible, whereas the fast current was not. 4. The reversible inhibition of the GABA-induced slow inward current produced by met-enkephalin or morphiceptin was naloxone (10(-5)-10(-4)M)-sensitive, whereas the irreversible block of the fast GABA response was not antagonised by naloxone. Some additive effects between GABA and the peptides were also noted. 5. The modulatory effect of the opioid peptides on the GABA response altered the peak current, the time-to-peak and inactivation time-course of the GABA-induced current. 6. Thus, the identified, isolated and internally perfused neurons of Lymnaea stagnalis L. provide a useful model for studying postsynaptic mechanisms of interaction between GABA and opioid peptides. This interaction is a phenomenon of evolutionary significance because of it is also found in mammals.

Characterization of responses to enkephalins and FMRFamide on B neurons of the cerebral ganglion of Aplysia

Abstract 1. Cerebral B neurons of Aplysia vary in reponse to leu- and met-enkephalin. Some neurons show inward currents to the enkephalins, while others show outward or biphasic currents. 2. The FMRFamide and acetylcholine responses also vary among the B neurons. 3. While acetylcholine and FMRFamide responses were usually accompanied by clear conductance changes and voltage dependency, those to the enkephalins often showed no conductance change and minimal voltage dependency. 4. The inward currents elicited by both the enkephalins and FMRFamide were increased by forskolin, an activator of adenylate cyclase, and by phosphodiesterase inhibitors.

Interaction of substance P and opiates in the CNS of Helix pomatia L.

Abstract 1. The present report demonstrates that substance P excites the RPal neuron. There is a delay in the onset of the substance-P-induced excitation: however, once achieved it is prolonged. 2. Morphine depresses the bursting activity of this neuron, an activity which can be blocked by naloxone. 3. Morphine, in a naloxone-reversible manner, can partially alter the excitatory effect of substance P on the RPal neuron. 4. The response of the RPal neuron to substance P depends on the physiological state of the organism. 5. The study demonstrates that substance P and opiates are acting on the same unit by different mechanisms. It also suggests the existence of a separate substance P receptor.