Cyclic AMP mediates inhibition of the Na(+)-K+ electrogenic pump by serotonin in tactile sensory neurones of the leech.
1. Serotonin (5-HT) reduced the after-hyperpolarization (AHP) amplitude in tactile sensory neurones (T) but not in pressor (P) or nociceptive (N) cells of the leech. 2. Adenylate cyclase activators, phosphodiesterase inhibitors and membrane permeant analogues of cyclic adenosine monophosphate (cyclic AMP) mimicked the effect of 5-HT in reducing the AHP amplitude in T neurones. 3. Ionophoretic injection of cyclic AMP in T cells reduced the AHP amplitude, while cyclic guanosine monophosphate (cyclic GMP) or adenosine-5'-monophosphate (AMP) were without effect. 4. Inhibition of adenylate cyclase by the drug RMI 12330A (also known as MDL 12330A) suggested that 5-HT reduced the AHP amplitude through cyclic AMP. 5. 8-Bromoadenosine-3'-5'-cyclic monophosphate (8-Br-cyclic AMP) was still able to reduce the AHP amplitude after blocking the Ca(2+)-activated K+ conductance with CdCl2 and converted the normal hyperpolarization which follows the intracellular injection of Na+ into a depolarization. In addition, the cyclic AMP analogue slowed down and reduced the repolarization usually induced by CsCl after perfusion with K(+)-free solution. It is proposed that, in T sensory neurones, cyclic AMP mediates the inhibition of the Na(+)-K+ electrogenic pump induced by 5-HT application.
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Dipartimento di Fisiologia e Biochimica G. Moruzzi, Università di Pisa, Italy.
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Brunelli
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D007097:Imines / Q000494:pharmacology; D007865:Leeches; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism* / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology*; D014110:Touch / Q000502:physiology*
D007097:Imines; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; C014925:RMI 12330A; D012964:Sodium; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D015056:1-Methyl-3-isobutylxanthine