Dale and Laidlaw (1912) demonstrated stimulation of the adrenal glands of the cat by pilocarpine, and Burn and Dale (1926) observed it after the injection of histamine. This action on the adrenal glands by both histamine and pilocarpine is partly responsible for the contractions of the normal and denervated nictitating membranes of the intact cat. But another factor seems to be involved in the response of the membranes, as Burn and Trendelenburg (1954) observed that sometimes the normal membrane responded more than the denervated membrane and that in some experiments the membranes responded after adrenalectomy. By perfusing the head of the cat with a Locke-dextran solution they demonstrated that both histamine and pilocarpine had no direct action on the nictitating membranes. The superior cervical ganglion of the normal side was not removed in their experiments on the whole animal and it thus seemed possible that these substances stimulated the ganglion. Dale and Laidlaw (1912) demonstrated the stimulation of the superior cervical ganglion of the cat by pilocarpine in the whole cat, and Ambache (1949) (Szczygielski, 1932). It was therefore decided to re-investigate the question of a stimulation of sympathetic ganglia by histamine and pilocarpine, using preparations in which the normal blood supply of the superior cervical ganglion was not interfered with. METHODSCats of 2 to 4 kg. were used. After inducing anaesthesia with ether, 80 mg. /kg. chloralose was injected intravenously. Intra-arterial injections were made into the central end of the lingual artery while occluding the external carotid artery. Thus the injected substance was diverted towards the superior cervical ganglion. With the exception of the internal carotid artery which was occasionally found and tied, no further attempts at isolation were made.The contractions of the nictitating membrane (and in some experiments of both membranes) were recorded with an isotonic lever fitted with a frontal writing point magnifying the movements of the membrane 7.5 times. The cervical sympathetic chain was cut. For preganglionic stimulation it was placed on a pair of shielded electrodes and covered with warm liquid paraffin. The stimulus had a frequency of 17/ sec. and a duration of 0.7 msec. The blood pressure was recorded from either the carotid artery of the other side or from the femoral artery.In some experiments spinal preparations were used, set up as described by Bum and Trendelenburg (1954). As the results with these preparations did not differ from those obtained under chloralose anaesthesia, they will not be mentioned separately.For arterial injection to adrenal glands, cats under chloralose anaesthesia were eviscerated and a cannula was tied into the central end of the coeliac artery. The aorta was tied below the kidneys. The blood pressure was recorded from the carotid artery.The following substances were used: histamine dihydrochloride or histamine acid phosphate, dissolved in saline and neutralized with N/10 NaOH, the dose being expressed as fre...
The mechanism of action of indirectly acting sympathomimetic amines was studied in the rat vas deferens, after inhibition of vesicular uptake (by reserpine), of MAO (by pargyline) and of COMT (by U-0521). 1. Km-values for the neuronal uptake of 12 substrates were determined as the IC50 of the unlabelled substrate inhibiting the initial rate of neuronal uptake of 0.2 mumol/l 3H-(-)-noradrenaline. The IC50 ranged from 0.35 mumol/l (for(+)-amphetamine) to 44.3 mumol/l (for 5-HT). The Vmax (determined for 8 substrates) was substrate-dependent. 2. Tissues were loaded with 0.2 mumol/l 3H-(-)-noradrenaline and then washed out with amine-free solution. All 12 substrates of uptake1 induced an outward transport of 3H-noradrenaline, and equieffective concentrations were positively correlated with Km. Moreover, the EC50 for release greatly exceeded Km. It is proposed that this discrepancy between EC50 and Km is indicative of the fact that at least four factors (each one in strict dependence on Km) contribute to the initiation of outward transport of 3H-noradreanline: a) the appearance of the carrier on the inside of the axonal membrane (facilitated exchange diffusion), b) the co-transport of Na+, c) the co-transport of Cl- (both lowering the Km for 3H-noradrenaline at the inside carrier), and d) inhibition of the re-uptake of released 3H-noradrenaline (through competition for the outside carrier). 3. At least for amezinium, Vmax appears to limit the maximum rate of outward transport. 4. For some substrates (especially for the highly lipophilic ones) bell-shaped concentration-release curves were obtained.(ABSTRACT TRUNCATED AT 250 WORDS)
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