Effects of cAMP on respiratory rhythm generation in brainstem-spinal cord preparation from newborn rat.
Involvement of cAMP in the generation of respiratory rhythm was studied in newborn rat brainstem-spinal cord preparations. The respiratory rhythm was monitored by C4 inspiratory activity and/or pre-inspiratory (Pre-I) activity of neurons in the rostral ventrolateral medulla; previously suggested to be primary rhythm generating neurons which have pacemaker properties. The effects of four cAMP-increasing agents (forskolin, IBMX, Db-cAMP, and 8-Br-cAMP) on this neuronal activity were examined. Perfusion with forskolin (3-10 microM) increased the burst rate of C4 inspiratory activity in 20 of 32 preparations, but in 8 of those the increase was preceded by transient depression. The facilitation of the respiratory rhythm was greater whenever the burst rate before forskolin treatment was lower. The Pre-I neuron burst rate, which was recorded together with C4 activity, predominantly increased with forskolin treatment. The effects of IBMX, Db-cAMP and 8-Br-cAMP were similar to those of forskolin, but they were slightly less potent. Long-lasting depression of the respiratory rhythm (C4 and Pre-I activity) by clonidine, which might decrease intracellular cAMP level via alpha 2-receptors, was reversed by forskolin. To investigate the direct effects of the cAMP-increasing agents on Pre-I neurons, Pre-I activity was isolated by blocking the chemical synaptic transmission by incubation in a low Ca solution (0.2 mM Ca2+, 5 mM Mg2+). Forskolin (5-10 microM), IBMX (5-10 microM), Db-cAMP (0.2-0.4 mM), and 8-Br-cAMP (0.4-0.75 mM) all enhanced the burst rate of isolated Pre-I neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Arata
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A
Department of Physiology, Showa University, School of Medicine, Tokyo, Japan.
Onimaru
H
H
Homma
I
I
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001933:Brain Stem / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000502:physiology*; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D005576:Colforsin; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine