Adrenergic modulation of the hypothalamic cholinergic mechanism in the control of emotional-defensive behavior in the cat.
(49/69)Effects of drugs influencing the activity of the hypothalamic noradrenergic system on the carbachol-induced emotional-defensive response were investigated. Intrahypothalamic injections of noradrenalin, amphetamine and reserpine did not produce any changes in cats' behavior. Injections of carbachol into the same hypothalamic loci, following the injections of noradrenalin, amphetamine or reserpine evoked all the characteristic symptoms of emotional-defensive behavior. However, a strong decrease in the number of growls and the duration of growling was observed when reserpine injections preceded the injections of carbachol into the same hypothalamic areas. Adrenergic alpha and beta agonists (methoxamine and isoprenaline) as well as antagonists (phentolamine and oxprenolol) when injected alone had no influence on the cats' behavior. Their effect on vocal responses evoked by subsequent injections of carbachol was not statistically significant. Results show that emotional-defensive behavior cannot be triggered by an activation of the hypothalamic noradrenergic system. However, emotional defensive behavior induced by cholinergic stimulation of the hypothalamus may be modified by changes in the activity of the hypothalamic noradrenergic system. (+info)
A comparison of the sensitivities of innervated and denervated rat vasa deferentia to agonist drugs.
(50/69)1. One vas deferens of a rat was denervated by stripping away the serous coat; the other vas was left intact as a control. One week later the sensitivity in vitro of both vasa deferentia to noradrenaline, adrenaline, dopamine, oxymetazoline or acetylcholine was measured.2. Log concentration response curves for the mean responses of both vasa from a group of four rats for each drug were plotted. Denervated vasa were more sensitive than control vasa to noradrenaline (16-fold), to adrenaline (8-fold), to dopamine (2-fold) and to oxymetazoline (2-fold). Denervated vasa were more sensitive to acetylcholine over the lower half of the concentration range only.3. It is concluded that these results support the theory that at least part of the increased sensitivity of denervated smooth muscle to catecholamines is due to an abolition or reduction of the neuronal uptake process. There is also a small non-specific increase in sensitivity. (+info)
Acceleration of noradrenaline biosynthesis in the guinea-pig vas deferens by potassium.
(51/69)1. Increasing the concentration of KCl in Krebs-Henseleit bicarbonate solution enhanced the formation of (14)C-noradrenaline ((14)C-NA) from (14)C-tyrosine in the guinea-pig vas deferens. In 52 mM KCl Krebs-Henseleit solution the specific activity of the newly formed (14)C-NA was double that of controls.2. The rate of synthesis of (14)C-NA from (14)C-tyrosine was constant for up to 2 h in 52 mM KCl Krebs-Henseleit solution and for 4 h in unmodified Krebs-Henseleit solution.3. There was no increase in NA formation in the presence of KCl rich Krebs-Henseleit solution if (14)C-DOPA was used as the starting substrate instead of (14)C-tyrosine.4. The specific activity of (14)C-tyrosine in the high KCl treated vas deferens was 80% of that of control tissues. Thus the enhanced synthesis of (14)C-NA in high KCl Krebs-Henseleit solution did not arise from an increase in the specific activity of precursor.5. The effect of K(+) on NA synthesis was not mimicked by ganglionic stimulants nor blocked by tetrodotoxin.6. Removal of Ca(2+) ions or increasing the concentration of Mg(2+) ions abolished the increase in synthesis of NA seen in high KCl Krebs-Henseleit solution but left the basal rate of NA synthesis in unmodified Krebs-Henseleit solution unaltered.7. The spontaneous release of newly synthesized catecholamines ((14)C-labelled) or tritiated noradrenaline ((3)H-NA) from vasa deferentia was increased in 52 mM KCl Krebs-Henseleit solution. Removal of Ca(2+) ions reduced the increased efflux of newly synthesized amine in high KCl media to that seen in unmodified Krebs-Henseleit solution. The efflux of (3)H-NA was reduced to one-third of its former rate in the absence of Ca(2+).8. High KCl Krebs-Henseleit solution caused a substantial contraction of the vas deferens which was not abolished by tetrodotoxin. Release of (3)H-NA paralleled the contractile response, and was likewise unaffected by tetrodotoxin.9. No evidence was obtained for any alterations in the activity of tyrosine hydroxylase, the rate limiting enzyme in the formation of NA from tyrosine, in homogenates of vas deferens which had been treated with 52 mM KCl Krebs-Henseleit solution.10. These results support the hypothesis that acceleration of NA synthesis occurs when tyrosine hydroxylase is freed from end-product inhibition by the release of noradrenaline, brought about in this case, by high concentrations of KCl. (+info)
The accumulation of guanethidine by human blood platelets.
(52/69)1. When human blood platelets were incubated aerobically in plasma containing 2 x 10(-7) to 10(-3)M radioactive guanethidine for 10 min to 6 hr, the drug was accumulated against a concentration gradient until concentration ratios (platelet/plasma) of up to 80:1 were obtained.2. The decline in rate of uptake after 3 hr appeared to result from a decrease in platelet viability, because accumulation was reduced by prolonged incubation before addition of guanethidine.3. Uptake was energy-dependent because it was inhibited by cold and ouabain.4. Sodium ions were essential for guanethidine uptake and retention of 5-hydroxytryptamine (5-HT).5. Accumulation was inhibited by 5-HT, desipramine, cocaine, dexamphetamine, bretylium, tyramine and noradrenaline; bethanidine, p-chlorophenylalanine and (-)-alpha-methyldopa were inactive.6. Guanethidine was tightly bound to platelets, only 10% being lost from labelled cells during 60 min incubation in drug-free plasma; but efflux was increased by addition of amphetamine.7. The binding sites for guanethidine seemed to be different from those for 5-HT since guanethidine accumulation was independent of 5-HT levels, and neither guanethidine uptake or release were affected by reserpine.8. Guanethidine was not metabolized by platelets or plasma in vitro.9. We consider that, if our results regarding uptake, binding and release of guanethidine are confirmed in vivo, and also found to apply to other pharmacologically active agents, then the eventual loss of a platelet-bound substance may increase pharmacological action by raising plasma levels. (+info)
A direct excitatory action of catecholamines on rat aortic baroreceptors in vitro.
(53/69)A persistent question with regard to the effects of catecholamines on baroreceptor activity has been whether the adrenergic action is indirectly mediated through an alteration in vessel wall tone or whether it is a direct action on the excitability of baroreceptor nerve endings. The effects of norepinephrine on the pressure-impulse frequency relationship of rat single aortic baroreceptor fibers were studied in vitro. Perfusion of the aortic arch with norepinephrine produced an excitatory response which consisted of: a drug-evoked stimulation of previously quiescent fibers at 0 mm Hg, and a sensitization of the response to pressure. The norepinephrine-induced facilitation was blocked by prazosin but not by yohimbine. Phenylephrine mimicked the effects of norepinephrine, whereas clonidine had no excitatory effects on baroreceptor activity. Baroreceptor activity was unaffected by beta-adrenergic agonists or antagonists. Norepinephrine had no effect on the pressure-volume relationship of the aortic arch, but produced a contraction of helical aortic strips. However, there was no correlation between the concentration-response relationship of norepinephrine on aortic smooth muscle and its excitatory action on baroreceptors. 5-Hydroxytryptamine and angiotensin II produced a contraction of helical strips, but had no effect on baroreceptor activity. Sodium nitrate reduced the norepinephrine-induced contractile response by 75%, but did not antagonize the baroreceptor facilitation. It is proposed that the excitatory action of norepinephrine is independent of smooth muscle activity, and is mediated by activation of alpha 1-adrenergic receptors located on the aortic baroreceptor nerve endings. (+info)
Cyclic nucleotides and their relationship to complement-component-C2 synthesis by human monocytes.
(54/69)The time courses of changes in cyclic nucleotide levels in monocytes have been studied. Histamine and prostaglandin E2 (PGE2) produced a rapid rise in cyclic AMP (peak 15 min) levels, which returned to normal within 4h, whereas cholera toxin, NaF and phosphodiesterase inhibitors produced slow sustained rises lasting over 24h. With the exception of isobutylmethylxanthine (10 mumol X 1(-1), none of these reagents altered cyclic GMP levels. alpha 1-Adrenergic and nicotinic cholinergic receptor-ligand interactions and imidazole produced rapid and relatively short-lived falls in cyclic AMP, and rises in cyclic GMP. In contrast, prostaglandin synthetase inhibitors produced delayed but more sustained falls in cyclic AMP but no rises in cyclic GMP. Agents that increased cyclic AMP decreased complement-component-C2 production, and those that decreased cyclic AMP increased C2 production. Agents that increased cyclic GMP alone (ascorbate, nitroprusside and prostaglandin F2 alpha) did not affect C2 production. Antigen-antibody complexes that stimulate C2 synthesis produced falls in cyclic AMP and rises in cyclic GMP similar to those produced by adrenergic and cholinergic ligands. Serum-treated complexes and anaphylatoxins, which inhibited C2 production, were associated with changes in cyclic AMP similar to those produced by histamine and PGE2. These data suggest that there are two transmembrane signals involved in the regulation of C2 production by monocytes. The inhibitory signal is adenylyl cyclase activation. The stimulatory signal is not so obvious, but may be Ca2+ influx, since the time courses of changes in cyclic nucleotides produced by agents that stimulate C2 synthesis are identical, and alpha 1-adrenergic agonists cause the formation of Ca2+ channels. (+info)
Effects of adrenergic and cholinergic drugs on electrical and mechanical activities of the rat cauda epididymidis in vitro.
(55/69)Electrical and mechanical activities of the rat epididymis (at 29 +/- 1.1 cm from the junction of the vas deferens) were recorded in vitro. The frequency of the spontaneous activity was 2.7 +/- 0.15/min. Adrenaline, phenylephrine, isoprenaline and carbachol increased the basal tension, frequency and amplitude of the contractions. Phentolamine, an alpha-adrenergic blocking agent, abolished the stimulatory effects of adrenaline and isoprenaline, but not those of carbachol. Propranolol and metoprolol, beta-adrenergic blocking agents, did not inhibit the stimulatory effects of isoprenaline. Atropine abolished the response to carbachol. The results suggest that alpha-adrenergic receptors but not beta-receptors are present in the rat epididymis. (+info)
Regional blood flow in canine brain during nicotine infusion: effect of autonomic blocking drugs.
(56/69)Radioactive microspheres (15 mu) were used to measure regional cerebral blood flow during intravenous infusion of nicotine (36 micrograms/kg/min) in anesthetized, open chest dogs. Experiments were conducted with uncontrolled mean aortic pressure and intact autonomic receptors (Series I; n = 9), and in four groups of dogs with mean aortic pressure held constant (Series II); 1) with intact autonomic receptors (n = 6), 2) after beta adrenergic blockade (n = 8), 3) after alpha and beta adrenergic blockade (n = 6), 4) after alpha and beta adrenergic and cholinergic blockade (n = 4). In Series I, nicotine raised mean aortic pressure (+ 72%) and increased flow in cerebral cortex (+ 67%), cerebellum (+ 38%), pons (+ 46%), medulla (+ 39%), and spinal cord (+ 48%). In all regions, but cortex, increases in vascular resistance limited nicotine-induced increases in flow. In Series II, nicotine changed flow only in cortex. Without blockade, nicotine increased cortical flow (+ 38%); but beta blockade abolished this increase in flow. After alpha and beta blockade nicotine again raised cortical flow (+ 29%), and additional cholinergic blockade had no effect on this response. It is concluded that nicotine causes predominant beta receptor mediated vasodilation in cerebral cortex, although it also activates alpha (vasoconstrictor) receptors and a non-adrenergic, non-cholinergic vasodilator mechanism in this region of brain. (+info)