Cyclic adenosine 3',5'-monophosphate mediates beta-receptor actions of noradrenaline in rat hippocampal pyramidal cells.
Intracellular recordings were made from rat hippocampal CA1 pyramidal neurones in the in vitro slice preparation to study the actions of cyclic adenosine 3',5'-monophosphate (cyclic AMP). Application of the membrane permeant analogue of cyclic AMP, 8-Br cyclic AMP caused a small depolarization of the resting membrane potential accompanied by an increase in membrane input resistance and also reduced the amplitude of depolarization-evoked calcium-activated potassium after-hyperpolarizations (a.h.p.s.). 8-Br cyclic AMP reduced calcium-activated a.h.p.s but did not reduce calcium action potentials in these cells. 8-Br cyclic AMP also reduced action potential frequency accommodation. The effects of 8-Br cyclic AMP were not mimicked by cyclic AMP applied extracellularly but were imitated by intracellular injections of cyclic AMP. Activation of the endogenous adenylate cyclase of pyramidal cells either by intracellular injection of the stable guanosine 5'-triphosphate (GTP) analogue guanylyl-imidodiphosphate, or by extracellular application of forskolin, reduced the a.h.p. and accommodation. Reducing phosphodiesterase activity with application of either 3-isobutyl-1-methylxanthine or Ro20-1724 reduced the amplitude of the a.h.p. and potentiated the a.h.p.-blocking action of noradrenaline. Reducing adenylate cyclase activity by application of SQ22,536 slightly increased the amplitude of the (a.h.p.) and reduced the a.h.p.-blocking action of noradrenaline. We conclude that the beta-receptor actions of NA on hippocampal CA1 pyramidal cells are mediated by intracellularly produced cyclic AMP.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000502:physiology; D051381:Rats
D000067956:Adenylyl Cyclase Inhibitors; C017759:9-(tetrahydro-2-furyl)-adenine; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D006165:Guanylyl Imidodiphosphate; D000242:Cyclic AMP; D000225:Adenine; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium; D015056:1-Methyl-3-isobutylxanthine; D009638:Norepinephrine