Adenosine agonists reduce voltage‐dependent calcium conductance of mouse sensory neurones in cell culture.

Abstract

SUMMARY1. Adenosine and several of its analogues produced a concentration-dependent shortening of calcium-dependent action potential (c.a.p.) duration of mouse dorsal root ganglion (d.r.g.) neurones in dissociated cell culture. The following rank order of potency was obtained: N6-(L-phenylisopropyl)adenosine > N6-(D-phenylisopropyl)adenosine > N6-cyclohexyladenosine > 2-chloroadenosine > 1-methylisoguanosine > adenosine. Effects of adenosine agonists on c.a.p. duration were blocked by methylxanthine adenosine antagonists. Adenosine monophosphate (AMP) and cyclic AMP shortened c.a.p.s in d.r.g. neurones, while ATP also depolarized cells.2. Voltage-clamp analysis revealed that the effect arose from reduction of a voltage-dependent calcium conductance. Adenosine agonists reduced depolarizationevoked inward currents but did not alter membrane conductance following blockade of calcium channels by cadmium. Additionally, adenosine reduced the instantaneous current-voltage slope (chord conductance) during step commands that produced maximal activation of voltage-dependent calcium conductance.3. If effects of adenosine on neuronal somata and synaptic terminals are similar, adenosine agonists may inhibit neurotransmitter release in the central nervous system by inhibiting a voltage-dependent calcium conductance. Since effects of adenosine agonists did not correspond with their relative potencies as modulators of adenylate cyclase activity or inhibitors of neurotransmitter release in peripheral tissues, a novel adenosine receptor may be involved in regulation of this conductance.

Modulation of inspiratory drive to phrenic motoneurons by presynaptic adenosine A1 receptors

“…Postsynaptically, adenosine hyperpolarizes cells by increasing a postsynaptic K+ conductance (Greene and Haas, 1985;Trussell and Jackson, 1985;Proctor and Dunwiddie, 1987;Gerber et al, 1989). Adenosine also inhibits voltage-dependent Ca*+ channels (MacDonald et al, 1986;Scholz and Miller, 1991;Mynlieff and Beam, 1994).…”

Effect of pertussis toxin on morphine, diphenhydramine, baclofen, clomipramine and physostigmine antinociception

“…Pertussis toxin-sensitive G-proteins represent the most widespread modulatory signaling pathway in neurones (Holz et al, 1986) and are responsible for inhibition of adenylate cyclase activity and modulation of several K + and Ca 2+ channels (Brown and Birnbaumer, 1990;Hepler and Gilman, 1992;Hille, 1994 Activation of opioid and et 2-adrenoceptors causes inhibition of adenylate cyclase activity and regulates ionic conductance, as documented by biochemical and electrophysiological studies (Sharma et al, 1975;Sabol and Nirenberg, 1979;Brown and Birnbaumer, 1990), via pertussis toxin-sensitive G-proteins (Childers, 1991;Aghajanian andWang, 1986, Dunwiddie andSu, 1988). Similarly, the stimulation of GABA B and adenosine A~ receptors provokes inhibition of adenylate cyclase in rat brain slices (Hill, 1985) and in cultured brain cells (Van Calker et al, 1979), the opening of several K + channels in central neurones (GS.hwiler and Brown, 1985;Trussel and Jackson, 1987) and a reduction of Ca 2+ currents in dorsal root ganglion cells (Dolphin and Scott, 1987;McDonald et al, 1986) by a pertussis toxin-inhibitable mechanism.…”

A1 Adenosine Receptors in Microglia Control Glioblastoma-Host Interaction

“…In the latter, A 1 AR is coupled to activation of K + channels (13) and inhibition of Ca 2+ channels (14), both mechanisms that attenuate neuronal excitability. By reducing excitotoxicity, adenosine can act as a neuroprotective factor.…”