cAMP activates an ATP-permeable pathway in neonatal rat cardiac myocytes

The molecular mechanisms associated withintracellular ATP release by the heart are largely unknown. In thisstudy the luciferin-luciferase assay and patch-clamp techniques wereused to characterize the pathways responsible for ATP release inneonatal rat cardiac myocytes (NRCM). Spontaneous ATP release by NRCMwas significantly increased after cAMP stimulation under physiologicalconditions. cAMP stimulation also induced an anion-selectiveelectrodiffusional pathway that elicited linear,diphenylamine-2-carboxylate (DPC)-inhibitable Cl currentsin either symmetrical MgCl₂ or NaCl. ATP, adenosine 5'-O-(3-thiotriphosphate), and the ATP derivatives ADP andAMP, permeated this pathway; however, GTP did not. The cAMP-induced ATPcurrents were inhibited by DPC and glibenclamide and by a monoclonalantibody raised against the R domain of the cystic fibrosistransmembrane conductance regulator (CFTR). The channel-like nature ofthe cAMP-induced ATP-permeable pathway was also determined by assessingprotein kinase A-activated single channel Cl and ATPcurrents in excised inside-out patches of NRCM. Single channel currentswere inhibited by DPC and the anti-CFTR R domain antibody. Thus thedata in this report demonstrate the presence of a cAMP-inducibleelectrodiffusional ATP transport mechanism in NRCM. Based on thepharmacology, patch-clamping data, and luminometry studies, the dataare most consistent with the role of a functional CFTR as the anionchannel implicated in cAMP-activated ATP transport in NRCM.

     

Effect of dissolved aromatic hydrocarbons on the growth of marine bacteria in batch culture.

Dissolved aromatic hydrocarbons were found to decrease growth rate and maximum cell density of marine bacteria in batch cultures. The magnitude of the decrement was observed to be a function of concentration of the hydrocarbon and inherent toxicity. The inherent toxicity was observed to increase inversely with solubility such that naphthalene at 100 muM concentration demonstrated a toxic effect similar to benzopyrene at 0.02 muM. A partial oxidation product of naphthalene was found to be more effective in decreasing growth parameters than naphthalene at equivalent concentrations and to cause complete cessation of growth at the higher concentrations permitted by its polar structure.     

Withdrawal from long-term benzodiazepine treatment.

Long-term, normal-dose benzodiazepine treatment was discontinued in 16 patients who were suspected of being dependent on their medication. The withdrawal was gradual, placebo-controlled, and double-blind. All the patients experienced some form of withdrawal reaction, which ranged from anxiety and dysphoria to moderate affective and perceptual changes. Symptom ratings rose as the drugs were discontinued, but usually subsided to prewithdrawal levels over the next two to four weeks. Other features of the withdrawal included disturbance of sleep and appetite and noticeable weight loss. Electroencephalography showed appreciable reduction in fast-wave activity as the drugs were withdrawn, and an improvement in psychological performance was recorded by the Digit Symbol Substitution Test. Because of the risk of dependence on benzodiazepines these agents should probably not be given as regular daily treatment for chronic anxiety.     

Controlled trial of trimipramine,monoamine oxidase inhibitors,and combined treatment in depressed outpatients.

A study was carried out in which 135 mildly or moderately depressed outpatients were randomly allocated to one of five groups receiving six weeks'' treatment weith antidepressant drugs. The groups received a tricyclic antidepressant (trimipramine; mean dose 106 mg at night) or a monoamine oxidase inhibitor (MAOI) (phenelzine or isocarboxazid; mean doses 45 and 32 mg/day respectively), or a combination of the two (phenelzine plus trimipramine or isocarboxazid plus trimipramine). Various scales were used to measure depression before and at one, three, and six weeks of treatment, and results were assessed blindly. The tricyclic antidepressant was found to be consistently superior to the MAOIs and the combined treatments. Some differential indicators of response to the various antidepressants were found--for example, patients with initial complaints of dizziness, suicidal ideas, irritability, and insomnia and a longer duration of illness were more likely to respond to trimipramine--but these were of only modest significance. Side effects were not troublesome in any group. It is concluded that neither MAOIs nor MAOIs combined with tricyclic antidepressants are the treatment of first choice in unselected outpatients with mild or moderate depression.     

Response to Propranolol and Diazepam in Somatic and Psychic Anxiety

A total of 12 chronically anxious psychiatric outpatients were treated with racemic propranolol (Inderal), diazepam (Valium), and placebo for one week each, using a balanced cross-over experimental design. Six patients had predominantly somatic anxiety, complaining mostly of bodily symptoms, and six had mainly psychic anxiety, complaining primarily of psychological symptoms. Clinical ratings of anxiety were made by patient and psychiatrist after each treatment. Though diazepam was in general more effective than propranolol or placebo in relieving anxiety, propranolol was more effective than placebo in patients with somatic anxiety but not in those with psychic anxiety. We suggest that propranolol should be reserved for patients whose anxiety symptoms are mainly somatic.