PubMed Health⌕ Search

Biomedical subjects

R J McIsaac

Publications and source records attributed to R J McIsaac.

At least 19 recordsLinked to original sources
PubMed1984

Facilitation of ganglionic response to bethanechol by repetitive stimulation of the preganglionic nerve.

Repetitive stimulation of the preganglionic nerve of the rat superior cervical sympathetic ganglion potentiates the amplitude of asynchronous firing elicited by the muscarinic agonist, bethanechol. The amplitude of stimulus-induced facilitation is not related to frequency of stimulation and occurs with a stimulation frequency of 10 Hz or greater. Facilitation, but not the asynchronous firing is reduced by lowering the temperature of the bathing solution. Dibutryl cyclic adenosine monophosphate and theophylline had no effect on asynchronous firing but reduced stimulus-induced facilitation. Neither dibutryl cyclic guanosine monophosphate up to 1 mM nor nitroprusside had any significant effect on bethanechol-induced asynchronous firing or stimulus-induced facilitation. Tetraethylammonium caused a 200% increase in stimulus-induced facilitation. Acetylcholine, in a concentration that elicited maximum nicotinic firing, had no effect on the magnitude of bethanechol-induced asynchronous firing. Increased Ca++, Mg++ or Mn++ reduced both asynchronous firing and stimulus-induced facilitation. It is concluded that facilitation is a result of transmitter release, possibly not acetylcholine.

Acetylcholine↗
PubMed1981

A comparison of cyclic guanosine 3':5'-monophosphate and muscarinic excitatory responses in the superior cervical ganglion of the rat.

The relationship between the magnitude of atropine-sensitive afterdischarge (AD), which is generated from slow excitatory postsynaptic potentials and the ganglionic cyclic guanosine 3':5'-monophosphate (cGMP) concentration was investigated in the rat superior cervical ganglion in vitro. Parallel increases in the magnitude of atropine-sensitive AD and cGMP concentration occurred with increasing frequency of preganglionic nerve stimulation up to 40 Hz for 10 sec. However, AD was completely antagonized by atropine, 0.1 to 1 microM, whereas the cGMP response was not significantly affected by up to 25 microM atropine. Although bethanechol, 0.5 mM, causes an asynchronous firing which can be recorded from the postganglionic nerve, bethanechol had no effect on the ganglionic cGMP concentration even in ganglia preincubated with the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, 1 mM. The methylxanthine did increase the resting cGMP concentration and the concentration of cGMP immediately after stimulation of the preganglionic nerve. It is concluded that muscarinic AD and the slow excitatory postsynaptic potentials of rat sympathetic ganglia are not generated by a mechanism involving an increase in ganglionic cGMP.

1-Methyl-3-isobutylxanthine↗
PubMed1979

Potentiation and inhibition of ganglionic transmission by ruthenium red.

The effect of ruthenium red, 2.5 to 5 muM, on ganglionic transmission in rat superior cervical ganglia and frog abdominal ganglia were studied in vitro. In rat ganglia, ruthenium red caused a spontaneous firing of ganglia cells, and an increase in the amplitude and duration of the compound action potential following a single stimulus volley. However, transmission following a conditioning volley or a repetitive stimulus train to the preganglionic nerve was depressed up to 60 sec. The asynchronous firing caused by bethanechol was potentiated by ruthenium red. In the frog, ruthenium red caused repetitive firing of ganglion neurons following either orthodromic or antidromic stimulation. It is suggested that the potentiation of the single potential and the spontaneous firing are due to a ruthenium red-induced increase in intracellular calcium concentration. The depression of transmission may be due to a temporary depletion of readily releasable acetylcholine. It is also suggested that ruthenium red has an effect on the postsynaptic membrane.

Action Potentials↗
PubMed1978

Effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate on sympathetic ganglionic transmission in rats.

The effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate (DBcAMP) on the amplitude of the postganglionic action potential during and after a 10 Hz repetitive volley, and 50 to 1000 msec after a conditioning stimulus were investigated. The effects of both drugs on some electrophysiological properties of single cells of the isolated superior cervical ganglia of rats were also studied. At low concentrations of theophylline a reversible potentiation of the compound action potential occurred during and after repetitive stimulation at 10 Hz and also after the single conditioning stimulus. This effect was antagonized by atropine. Large concentrations of theophylline exerted a depressive effect only. Low concentrations of DBcAMP caused a reversible initial depression followed by a durable facilitation of transmission during repetitive stimulation. These concentrations potentiated the action potential amplitude after repetitive stimulation, but depressed it after a single conditioning stimulus. Atropine augmented the latter two effects. DBcAMP at large concentrations depressed transmission, but transmission was facilitated after drug washout. Theophylline and guanosine 3':5'-monophosphate, at ineffective concentrations when used singly, potentiated each other and elicited facilitation which was abolished by atropine. Theophylline and DBcAMP at these concentrations depolarized ganglion cells with a time course shorter than that of the aforementioned effects. Both drugs reduced the frequency and amplitude of the spontaneous miniature excitatory postsynaptic potentials. Theophylline did not increase the evoked transmitter release appreciably. On the basis of these findings and the evidence from literature, it is suggested that the reversible facilitatory effect of theophylline may be at least in part due to inhibition of phosphodiesterase of the ganglion cells leading to an enhanced muscarinic transmission. The prolonged facilitatory effect of DBcAMP may result from a durable change in the postsynaptic membrane structure leading to enhanced muscarinic transmission. An enhancement in the muscarinic transmission by both drugs increases the membrane excitability causing recruitment of subthreshold depolarized cells to discharge resulting in facilitation.

Acetylcholine↗
PubMed1978

Ganglion blocking effects of streptomycin.

The effects of streptomycin on the postganglionic compound action potential, presynaptic nerve terminal spike and preganglionic nerve action potnetial were studied in rabbit and rat superior cervical gnaglia. Streptomycin had a dose-dependent, blocking effect on the postganglionic action potential. The drug was found to have a preferential blocking effect on the first spike, S1, of the compound postganglionic action potential, but the second, S2, major spike was depressed at higher concentrations. At 1 mg/ml, streptomycin reduced the amplitude of the presynaptic nerve terminal action potential, but had no significant effect on the action potential recorded from the cervical sympathetic preganglionic nerve. Increasing the concentrations of Ca++ in the bathing solution antagonized the blocking effect of the antibiotic on the postganglionic action potential. The results are interpreted as indicating that ganglionic blockade by streptomycin is due, mainly, to a presynaptic effect which results in a decreased release of acetylcholine.

Action Potentials↗
PubMed1978

Post-tetanic enhancement of stimulus-induced muscarinic afterdischarge in the rat superior cervical ganglion.

The enhancement of asynchronous muscarinic ganglionic firing which follows a preganglionic nerve stimulus volley by high frequency repetitive conditioning stimuli was studied in the rat isolated superior cervical ganglion. Muscarinic afterdischarge which occurred in chlorisondamine-blocked ganglia was enhanced for up to 1 hr after a 40 Hz conditioning volley lasting 7.5 to 30 sec. Enhancement did not occur when release of acetylcholine was blocked by reducing the calcium in the modified Krebs' solution or when magnesium or manganese chlorides were added to the saline during the conditioning period. Metabolic inhibitors, dinitrophenol, sodium azide and ouabain, blocked the enhancement process but not the asynchronous muscarinic firing. Phenytoin, 10(-6) M, did not reduce the enhancement of firing. Dopamine, 5 X 10(-5) M, had no effect on muscarinic afterdischarge, but dibutyryl cyclic adenosine 3':5'-monophosphate, 5 and 10 X 10(=3) M, caused a 43 and 53% increase in the maximum amplitude of afterdischarge. Dibutyryl cyclic guanosine 3':5'-monophosphate had no effect on post-tetanic enhancement or afterdischarge in concentrations up to 1 X 10(-3) M. A working hypothesis is proposed: following a conditioning stimulus, a prolonged postsynaptic change occurs which results in an increased responsiveness to muscarinic agonists, and this change probably involves a metabolic reaction since it is reduced by metabolic inhibitors. Evidence to support the concept that dopamine is a modulator of enhancement in the rat superior cervical ganglion was not obtained.

Animals↗
PubMed1977

Afterdischarge on postganglionic sympathetic nerves following repetitive stimulation of the preganglionic nerve to the rat superior cervical ganglion in vitro.

An asynchronous firing or afterdischarge (AD) was recorded in vitro from the postganglionic internal carotid nerve of the rat superior cervical ganglion following repetitive stimulation of the preganglionic nerve when ganglion transmission was blocked by chlorisondamine, nicotine or hexamethonium, but was rarely observed in untreated ganglia. A stimulus frequency of at least 5 Hz was required to induce AD and as few as 100 pulses caused a significant response. The amplitude and duration of AD varied with the number of pulses. Low calcium solutions resulted in AD in the absence of ganglion blocking drugs, and high calcium solutions or low concentrations of atropine abolished the AD. Increasing magnesium concentration to 10 mM or the manganese concentration to 0.1 mM reduced or prevented AD following preganglionic nerve stimulation. The onset of AD was delayed in potassium-free solutions and at a lowered temperature. Dinitrophenol had a small depressant effect on AD but sodium azide reduced the amplitude significantly. Exposure of ganglia to bethanechol, 300 to 600 muM, resulted in asynchronous firing recorded from postganglionic nerves, and stimulation of the preganglionic nerve transiently depressed the drug-induced firing but enhanced the firing 30 to 60 seconds after the volley. Physostigmine did not alter the amplitude of bethanechol-induced firing after a volley. Prolonged high frequency (40 Hz) stimulation of the preganglionic nerve increased the AD following a 20 Hz test volley for up to 1 hour. It is concluded that increasing the release of acetylcholine or blockade of nicotinic receptors makes more acetylcholine available for interaction with muscarinic receptors, and that stimulation of the preganglionic nerve unmasks or sensitizes ganglionic muscarinic receptors. No clear evidence of a metabolic basis for the muscarinic response was obtained.

Animals↗
PubMed1974

Effect of preganglionic nerve stimulation on sensitivity of the superior cervical ganglion to nicotinic blocking agents.

1 Periodic stimulation (every 10 min) of the cervical sympathetic nerve increased the ganglionic block by low concentrations of chlorisondamine (CHL) in the superior cervical ganglion of the cat when compared to the contralateral unstimulated side.2 Periodic stimulation of the postganglionic nerve was ineffective in increasing the block.3 Ganglionic block by low concentrations of mecamylamine had the same stimulus dependency, but ganglionic block by any dose of hexamethonium was not influenced by nerve stimulation.4 Physostigmine infused together with CHL increased the rate of onset of block produced by CHL. Atropine had no apparent effect on the development of ganglionic block by CHL.5 Repeated intra-arterial injections of 1,1-dimethyl-4-phenylpiperazinium into the circulation of the superior cervical ganglion increased the magnitude of block produced by CHL. Similar injections of methacholine had no effect on ganglionic block produced by CHL.6 The results are interpreted to indicate that activation of ganglionic nicotinic receptors increased the affinity of receptors for CHL and mecamylamine.

Animals↗