Microiontophoretic studies of the effects of cyclic nucleotides on excitability of neurones in the rat cerebral cortex

Abstract

SUMMARY1. Responses of cerebral cortical neurones to the microiontophoretic application of acetylcholine, noradrenaline, cyclic adenosine 3',5'-monophosphate (cyclic AMP) and cyclic guanosine 3',5'-monophosphate (cyclic GMP) were examined.2. The application of acetylcholine and cyclic GMP to identified pyramidal tract neurones resulted in an increased frequency of firing in a large number of cells. Upon application of both substances to cells which could not be identified as pyramidal tract cells, a reduction in the frequency of spontaneous firing was sometimes observed.3. Careful current controls had no effect on the cells discussed here, indicating that the observed responses were not due to the iontophoretic currents. Also, the electro-osmotic ejection of cyclic GMP (outward current) produced similar changes of cell firing to those which followed iontophoretic application (inward current).4. The microiontophoretic application of atropine resulted in a blockade of acetylcholine responses while leaving responses to cyclic GMP unaffected. This suggests that cyclic GMP was not acting indirectly by releasing acetylcholine from presynaptic endings.5. Ejection of cyclic GMP from solutions containing calcium ions produced responses comparable to those produced by cyclic GMP alone. It

Blockade of Striatal Neurone Responses to Morphine by Aminophylline: Evidence for Adenosine Mediation of Opiate Action

“…in fact, demonstrated several opiate/opioid receptors in brain, at least one of which is not readily blocked by naloxone (the 6-enkephalin receptor) (Lord, Waterfield, Hughes & Kosterlitz, 1977). As the corpus striatum is an area rich in enkephalins, and able to synthesize them (Hughes, Kosterlitz & McKnight, 1978) (Dingledine et al, 1978 (Blume et al, 1973;Gintzler & Musacchio, 1975;Sawynok & Jhamandas, 1976;Green & Stanberry, 1977;Okwuasaba, Hamilton & Cook, 1977;Stone & Taylor, 1977) and our results are therefore consistent with the hypothesis that a consequence of morphine's interacting with its receptor is a release of adenosine, which then combines with its receptor to produce the well-documented depression of firing observed here (Phillis et al, 1974;Kostopoulos & Phillis, 1977;Stone & Taylor, 1977;Taylor & Stone, 1978).…”

4‐aminopyridine Blockade of Neuronal Depressant Responses to Adenosine Triphosphate

“…viously (Phillis et al, 1974;Kostopoulos & Phillis, 1977;Stone & Taylor, 1977;1978a, b;Taylor & Stone, 1978; and support the view that these compounds may act to modulate neuronal activity, whether or not they are released as neurotransmitters (Burnstock, 1972;Stone, 1978).…”

“…Various purine derivatives such as adenosine, adenosine monophosphate (AMP) and triphosphate (ATP) powerfully depress the firing rate of single neurones in the central nervous system when applied by microiontophoresis (Phillis, Kostopoulos & Limacher, 1974; Kostopoulos & Phillis, 1977;Stone & Taylor, 1977, 1978aTaylor & Stone, 1978;. The mechanism of this effect is unclear but in several tissues adenosine or ATP increase cell membrane potassium permeability (de Grubareff & Sleator, 1965;Burnstock, 1972;Tomita & Watanabe, 1973;Burgess, Claret & Jenkinson, 1979;Hartzell, 1979) and a similar effect on central neurones could account for the depression of firing rate.…”

Synaptic delay in the heart: an ionophoretic study.

“…Several intracellular processes have been postulated to mediate muscarinic responses. These include synthesis of cyclic GMP (Greengard, 1976;Stone & Taylor, 1977), breakdown of phosphatidylinositol (Michell, 1975) and release of calcium ions (Berridge, 1975). Direct proof of the necessary involvement of any of these events in muscarinic responses is lacking, nor is it possible to say precisely how they might contribute to the long latency.…”