Effects Of Adrenoceptor Agonists Research Articles

Alpha 2-adrenoceptors inhibit the cholera-toxin-induced intestinal fluid accumulation.

The effects of adrenoceptor agonists and antagonists on the cholera-toxin-induced intestinal fluid accumulation and the mucosal levels of cAMP were investigated in vivo. Cholera toxin produced a marked fluid accumulation. Adrenaline inhibited the effect of the toxin in a dose-dependent manner. An alpha 2-adrenoceptor blocking agent yohimbine antagonized the effect of adrenaline. The alpha 1-adrenoceptor blocking agents prazosin and phenoxybenzamine failed to antagonize the effect of adrenaline. A high dose of a beta-adrenoceptor blocking agent pindolol did not antagonize the effect of adrenaline. Yohimbine or pindolol alone did not produce any effects on the toxin-induced fluid accumulation. However, prazosin and phenoxybenzamine per se inhibited the toxin-induced fluid accumulation. An alpha 2-selective agonist clonidine was slightly more potent than adrenaline, and was about 100-fold more potent than the alpha 1-selective agonist methoxamine in inhibiting the cholera-toxin-induced intestinal secretion. Clonidine, adrenaline and methoxamine failed to reduce the mucosal levels of cAMP, while these alpha-adrenoceptor agonists inhibited the toxin-induced fluid accumulation in the same preparations. These results suggest that the stimulation of alpha 2-adrenoceptors inhibit the cholera-toxin-induced intestinal secretion without reducing the whole mucosal levels of cAMP.

The role of calcium in the effects of noradrenaline and phenoxybenzamine on adrenergic transmitter release from atria: no support for negative feedback of release.

1 The relation of calcium ion influx into nerve terminals to presynaptic adrenoceptor function and the possible masking, by desensitization due to intraneuronal calcium accumulation, of the effects of adrenoceptor agonists and antagonists on presynaptic alpha-adrenoceptors was investigated in guinea-pig atria previously incubated with [(3)H]-noradrenaline.2 Atria were stimulated with 100 pulses at various frequencies (1 to 15 Hz) in standard (2.3 mm), low (0.26 mm) and high (6.9 mm) calcium-Krebs solution in the absence and then the presence first of noradrenaline and subsequently phenoxybenzamine.3 The per pulse overflow of tritium was directly related to the calcium concentration of the Krebs solution, being much reduced and substantially increased in 0.26 and 6.9 mm calcium-Krebs solutions respectively.4 Noradrenaline inhibited the overflow of tritium in low calcium-Krebs solution, to a relatively constant extent, independently of frequency. In addition, the agonist had a greater maximal inhibitory effect in standard than in reduced calcium-Krebs. The catecholamine was as effective an inhibitor of overflow at the lowest and highest frequencies in high as it was in standard calcium-Krebs solution. Phenoxybenzamine invariably increased the tritium overflow but was generally less effective both in low and in high calcium-Krebs solution. The patterns of inhibition and enhancement of stimulation-induced tritium overflow by these two agents do not indicate an intimate relationship between calcium influx and adrenoceptor activation; nor does desensitization appear to be an adequate explanation of the relationship between frequency of stimulation and the intensity of agonist and antagonist effect in the three different calcium concentrations.5 It is concluded that the perineuronal levels of adrenergic transmitter do not establish the magnitudes of effect of exogenous adrenoceptor agonists and antagonists on tritium overflow and that a negative feedback regulation of release by transmitter is exceedingly unlikely under ordinary conditions of neurotransmission.

The distribution of adrenoceptors and other drug receptors between the two ends of the rat vas deferens as revealed by selective agonists and antagonists.

1. The effects of adrenoceptor agonists and other agonists on the contractile responses of the prostatic and epididymal portions of the rat isolated vas deferens to single pulse field stimulation were investigated. 2. alpha-Adrenoceptor agonists produced prejunctional alpha 2-mediated inhibition and post-junctional alpha 1-mediated potentiation of the nerve-induced responses. Guanabenz and xylazine produced mainly inhibitory effects, xylazine being 10 times less potent. Clonidine and oxymetazoline produced inhibition with similar potency to guanabenz but at higher concentrations excitatory effects were present, particularly in the epididymal portion. Phenylephrine produced only potentiation of the nerve-induced response in both portions. Potentiation of nerve-induced responses was a more sensitive and quantitative index of excitation than was direct contraction of the tissue. 3. Isoprenaline and salbutamol both gave beta 2-mediated inhibition of the nerve-induced responses in both portions of tissue. At least part of the effect was post-junctional since phenylephrine contractions were inhibited. Isoprenaline also produced a post-junctional alpha 1-mediated excitation. 4. Noradrenaline produced effects qualitatively similar to those of the other alpha-adrenoceptor agonists, inhibition and excitation predominating in the prostatic and epididymal ends respectively. 5. Morphine produced inhibition in the mouse but not in the rat vas deferens. In rat vas, however, enkephalin analogues produced pre-junctional inhibition of responses in both portions which could be partly reversed by naloxone; restoration of the adrenergic component was more complete. Rat anococcygeus showed no equivalent effect. 6. Adenosine 5'-triphosphate (ATP) inhibited nerve-induced responses in each portion with a greater effect on the prostatic portion.

Effects of adrenaline and isoprenaline on hepatic venous haemodynamics and venous return in the dog.

1. The effects of adrenoceptor agonists on venous haemodynamics were examined, utilizing the lower half perfusion method in dogs. 2. Femoral arterial pressure, central venous pressure, thoracic vena caval flow, abdominal vena caval flow, renal venous flow and femoral venous flow were measured simultaneously usning electronic transducers and electromagnetic flow-meters. Hepatic volume change was monitored by the strain-guage arch. 3. Single injections of both adrenaline (1.0 microgram/kg) and isoprenaline (1.0 microgram/kg) intra-aortically produced an increase in venous return, adrenaline transiently and isoprenaline continuously. 4. Epinephrine increased hepatic venous flow, while isoprenaline increased only abdominal vena caval flow. 5. These findings suggest that effects of alpha-adrenoceptors are more pronounced on the hepatic vein, while on other peripheral veins, effects of beta-adrenoceptors are more pronounced.