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Biomedical subjects

M J Rand

Publications and source records attributed to M J Rand.

At least 163 records · Page 9Linked to original sources
PubMed1974

Effects of the muscarinic agonist McN-A-343 on the release by sympathetic nerve stimulation of (3H)-noradrenaline from rabbit isolated ear arteries and guinea-pig atria.

1 McN-A-343 (4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride) in concentrations of 10(-5) and 10(-4)M inhibits the stimulation-induced efflux of radioactivity from segments of rabbit ear artery that have previously been incubated with (-)-[(3)H]-noradrenaline, and also decreases the contractile response.2 The inhibitory effects of McN-A-343 (10(-5)M) on the efflux of radioactivity and the contractions induced by low frequencies of stimulation (2 and 5 Hz) are reversed by atropine, but atropine does not modify these effects with high frequencies of stimulation (20 and 50 Hz).3 McN-A-343 (10(-4)M) enhances the stimulation-induced efflux of radioactivity from guinea-pig atria that have previously been incubated with (-)-[(3)H]-noradrenaline, and prolongs the positive inotropic response. These effects are not modified by atropine.4 It is concluded that McN-A-343 has different effects on adrenergic transmitter release in the two tissues. In the artery, it acts as an agonist on muscarinic receptors of adrenergic terminals to inhibit transmitter release at low frequencies of stimulation. In the atria it enhances transmitter efflux from the tissue, largely by inhibiting re-uptake.

Alkynes↗
PubMed1973

Comparison of effects of six cholinomimetic drugs on inhibition of uptake of 3 H-( )-noradrenaline by guinea-pig atria.

The effects of N,N-dimethyl-N'-phenyl-piperazinium (DMPP), 4-(m-chlorophenyl-carbamoyloxy) - 2 - butynyltrimethylammonium chloride (McN-A-343), pilocarpine, acetylcholine, methacholi-ne and nicotine in inhibiting the uptake of (3)H-(+/-)-noradrenaline by guinea-pig atria were compared. In concentrations of 1 x 10(-4)M, the percentage inhibitions were as follows: DMPP, 89.1%; McN-A-343, 78.7%; pilocarpine 43.5%; acetylcholine, 35.7%; methacholine, 32.9%; nicotine, 21.6%.

Acetylcholine↗
PubMed1973

Acidaemia produced by spinal stimulation in the pithed rat.

1. Electrical stimulation of the thoraco-lumbar spinal nervous outflow in the pithed rat preparation produces a fall in arterial blood pH.2. A component of the acidaemic response results from stimulation of skeletal muscle, since the acidaemic response is reduced when contractions of muscle are blocked with gallamine.3. The residual acidaemic response in gallamine-treated rats is reduced by adrenalectomy, suggesting that catecholamines liberated from the adrenal medulla may mediate part of the effect.4. Guanethidine reduces the acidaemic response remaining in adrenalectomized, gallamine-treated rats, suggesting that the effect of noradrenaline released from sympathetic nerve endings contributes to the fall in pH.5. Neither phenoxybenzamine nor propanolol alone significantly reduces the acidaemic response in gallamine-treated rats, but a combination of the two antagonists almost abolishes the effect. Hence the acidaemia is mediated through effects of catecholamines on both alpha- and beta-adreno-receptors.6. Since acidaemia affects responses to sympathetic nerve stimulation and sympathomimetic amines, the significance of these observations is discussed with reference to the use of the pithed rat preparation for assessment of drugs affecting adrenergic mechanisms.

1-Propanol↗
PubMed1972

Depressor responses to spinal stimulation in the pithed rat.

1. Electrical stimulation of the spinal nerves in the pithed rat preparation produces a pressor response due to sympathetic vasoconstriction.2. When the vasoconstrictor effect of sympathetic stimulation is abolished by guanethidine or hexamethonium and the blood pressure is raised by noradrenaline infusion, spinal stimulation produces depressor responses or complex responses containing depressor components.3. Contractions of skeletal muscle caused by stimulation of motor nerves result in complex changes in blood pressure consisting of a pressor component due to clamping of muscle blood vessels and a secondary depressor phase due to functional hyperaemia.4. The depressor response is partly due to stimulation of cholinergic postganglionic fibres. The acetylcholine released, which causes vasodilatation, may be the overflow from neuromuscular junctions or ganglionic synapses.5. Stimulation of the nerves to the adrenal medulla causes release of adrenaline which has a vasodilator effect during noradrenaline infusion.

Adrenalectomy↗
PubMed1972

Effects of McN-A-343 and DMPP on the uptake and release of 3 H-noradrenaline by guinea-pig atria.

1. McN-A-343 4-(m-chlorophenylcarbamoyloxy)-2-butynyltrimethylammonium chloride and DMPP (N,N-dimethyl-N'-phenylpiperazinium iodide) inhibit the uptake of (+/-)-(3)H-noradrenaline by guinea-pig atria, being approximately as potent as cocaine in this respect.2. The inhibition of uptake produced by McN-A-343 or DMPP was not affected by atropine or hexamethonium in concentrations which antagonized actions on muscarinic and nicotinic receptors respectively.3. McN-A-343 in the presence of atropine had a positive inotropic action on atria, but this was not accompanied by efflux of radioactivity from atria previously incubated with (-)-(3)H-noradrenaline.4. In the presence of McN-A-343, responses of atria to noradrenaline were increased and those to tyramine were decreased.5. DMPP had positive inotropic and chronotropic actions on atria, and these effects were accompanied by an increase in efflux of radioactivity from atria previously incubated with (-)-(3)H-noradrenaline.

Animals↗