Elevation of intracellular cyclic AMP concentration fails to inhibit adrenaline-induced hyperpolarization in amphibian sympathetic neurons.
1. The effect of drugs on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of desmethylimipramine (DMI)-treated bullfrog paravertebral sympathetic ganglia was studied by radioimmunoassay. The adrenaline-induced hyperpolarization (Adh) in the tissue was recorded by means of the sucrose-gap technique. 2. In the presence of propranolol (1 microM) and DMI (0.5 microM), adrenaline (1 microM) significantly reduced the concentration of cyclic AMP in forskolin-treated ganglia. This effect was prevented by pertussis toxin (5 micrograms ml-1). 3. The relative potency for drugs which increased ganglionic cyclic AMP content was: 50 microM forskolin much greater than 5 mM fluoride greater than 2 mM fluoride greater than 2 mM isobutylmethylxanthine (IBMX) greater than 5 mM caffeine. In contrast, their relative potency for inhibition of the Adh was: 2 mM IBMX greater than 5 mM fluoride greater than 5 mM caffeine much greater than 2 mM fluoride greater than 50 microM forskolin. The Adh was unaffected by pertussis toxin (5 micrograms ml-1). 4. Although the Adh was slightly reduced by the extracellular application of 8-bromo (8-Br) cyclic AMP, the majority of the data suggest that the transduction mechanism underlying the Adh is independent of the intracellular cyclic AMP concentration and provide an example of an alpha 2-adrenoceptor-mediated response that occurs independently of inhibition of adenylate cyclase.
Zidichouski
J A
JA
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Kehoe
M P
MP
Wong
K
K
Smith
P A
PA
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D004837:Epinephrine / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009467:Neuromuscular Depolarizing Agents; D009474:Neurons / Q000187:drug effects*; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011892:Rana catesbeiana; D013564:Sympathetic Nervous System / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000378:metabolism
D037361:Adenylate Cyclase Toxin; D009467:Neuromuscular Depolarizing Agents; D010726:Phosphodiesterase Inhibitors; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D004837:Epinephrine