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Biomedical subjects

G Kunos

Publications and source records attributed to G Kunos.

At least 127 records · Page 7Linked to original sources
PubMed1979

Naloxone reverses the antihypertensive effect of clonidine.

In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.

Animals↗
PubMed1978

Adrenoceptors.

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Animals↗
PubMed1977

Thyroid hormone-dependent interconversion of myocardial alpha- and beta-adrenoceptors in the rat.

1 The effects of thyroid state on the properties of adrenoceptors mediating inotropic and chronotropic responses of the rat heart were assessed on the basis of the relative potencies of alpha- and beta-adrenoceptor agonists, the effects of alpha- and beta-adrenoceptor antagonists and the tissue uptake of [3H]-phenoxybenzamine ([3H]-PB). 2 In isolated, electrically driven left atria the ratio of the inotropic potencies of isoprenaline and phenylephrine and the inhibitory potency of propranolol (40nM-4 muM) were significantly reduced after thyroidectomy and were moderately increased after thyroxine treatment of control rats. 3 Block of inotropic responses to noradrenaline and to phenylephrine by PB (7.3 nM-7.3 muM) and the tissue uptake of [3H]-PB were significantly greater in preparations from thyroidectomized than in those from control or from thyroxine treated rats. alpha-Adrenoceptor inhibition by phentolamine (0.26-2.6 muM) also increased after thyroidectomy, and phentolamine effectively protected alpha-adrenoceptors from block by and binding of [3H]-PB. 4 The beta1-receptor antagonist H 93/26 (0.1 muM) significantly potentiated alpha-adrenoceptor blockade by PB in hypothyroid but not in control preparations. 5 In spontaneously beating right atria the chronotropic potency of agonists and the effects of antagonists were altered in the same way as were inotropic responses and the slope of the agonist concentration-response curves were significantly reduced after thyroidectomy. Effects of agonists and antagonists were not significantly influenced by thyroxine treatment. 6 Changes in the effects and tissue uptake of sympathomimetic drugs observed after thyroidectomy were reversed to or beyond control levels by thyroid hormone treatment of thyroidectomized animals. 7 The results presented are interpreted as indicating a thyroid hormone-dependent interconversion of myocardial alpha- and beta-adrenoceptors. It is suggested that this interconversion is similar to that observed earlier in frog hearts at different temperatures, and that both effects may reflect an allosteric transition between two forms of a single basic structure.

Animals↗
PubMed1977

Effects of sympathetic innervation and temperature on the properties of rat heart adrenoceptors.

1. The pharmacological characteristics of adrenoceptors at different temperatures were assessed on the basis of the effects of various alpha- and beta-adrenoceptor agonists and antagonists on electrically-driven left atria and spontaneously-beating pairs of atria from rats. 2. Phenoxybenzamine (Pbz) potentiated inotropic responses of left atria to noradrenaline (NA) at 31 degrees C, produced significantly less potentiation at 24 degrees C and inhibited responses at 17 degrees C; it had little effect on responses to CaCl2. Both Pbz and phentolamine inhibited responses to phenylephrine more effectively at 17 than at 31 degrees C. N-cyclohexylmethyl-N-ethyl-beta-chloroethylamine hydrochloride (GD-131), a haloalkylamine with negligible alpha-adrenoceptor blocking activity, caused only potentiation of responses to NA at 17 degrees C. 3. The presence of phentolamine during incubation with Pbz eliminated block of responses to NA and revealed a potentiation that was equivalent at all three temperatures tested. Phentolamine did not alter the block of responses to 5-hydroxytryptamine by Pbz. Protection of alpha-adrenoceptors by phentolamine during exposure to [3H]-Pbz significantly decreased the amount of label bound to the myocardium at 17 degrees C, but did not alter binding at 31 degrees C. 4. Inhibition of responses to NA by propranolol decreased with temperature, and the magnitude of the change increased with the concentration of propranolol. Compared to 31 degrees C, the effect of the highest concentration of propranolol. (4.0 micronM) was significantly decreased at 24 degrees C, and the effects of all except the lowest concentration (0.04 micronM) were significantly decreased at 17 degrees C. 5. The potency of isoprenaline decreased and that of phenylephrine increased at low temperatures, and their potency ratio was much lower at 17 than at 31 degrees C for both the inotropic and chronotropic responses of spontaneously-beating atria. However, the ratio was unaffected by temperature in electrically-driven left atria. A similar difference between spontaneously-beating and driven preparations is apparent in the data of other workers, but its basis is not clear. 6. Atria from rats pretreated with 6-hydroxydopamine (6-OHDA) were sensitized to the effects of NA, and there was no increase in alpha-adrenoceptor properties at low temperatures. Little alpha-adrenoceptor activity could be demonstrated in chemically denervated atria at any temperature, 6-OHDA pretreatment did not alter the binding of [3H]-Pbz at 31 degrees C, but decreased it significantly at 17 degrees C. Pretreatment with reserpine caused some sensitization, but not significantly after the characteristics of the adrenoceptors or their responses to temperature. 7. It is concluded that the adrenoceptors of atria are affected by temperature in much the same way as those of frog hearts, although the transition from beta- to alpha-adrenoceptor properties may begin at a slightly higher temperature...

Animals↗
PubMed1976

Temperature-induced interconversion of alpha-and beta-adrenoceptors in the frog heart.

1. The effect of ambient temperature on the properties of adrenoceptors mediating inotropic responses was assessed in isolated frog hearts on the basis of the effects and tissue uptake of alpha- and beta-adrenoceptor antagonists. 2. At temperatures of 23degree C and above inotropic responses to adrenaline were antagonized by propranolol (0-4-4-0muM), but were unaffected by phentolamine (26-5muM) and were potentiated by phenoxybenzamine (POB) (0-7-29-5muM). Below 17degree C the activity of propranolol was reduced at least tenfold, and the alpha-adrenoceptor antagonists inhibited responses to both adrenaline and isoprenaline, but not those to CaCL2. 3. The responses of hearts exposed to POB at 14degree C and then tested, after thorough washing, at both 14 and 24degree C were similarly inhibited at both temperatures, i.e. the usual beta-adrenoceptor response did not appear at the higher temperature. Conversely, exposure to POB at 24degree C produced only potentiation at both test temperatures. 4. Parallel to the reciprocal changes in their blocking actions, significantly more (14C)propranolol was retained by hearts exposed at high temperatures and significantly more (3H)POB was bound to the myocardium at low temperatures. Changes in binding and in the pharmaco logical effects of both blocking agents occurred entirely within a relatively narrow temperature range (17-22degree C) Parallel to the change from alpha- to beta-adrenoceptor characteristics with increasing temperature, the sensitivity of the hearts to adrenaline increased about tenfold. 5. Phentolamine (26-5muM) effectively protected hearts from block by (3H)POB at 14degree C, unmasked a potentiation of responses to adrenaline equivalent to that produced by POB at 24degree C, and reduced binding of the label to approximately the level found in unprotected hearts exposed at the higher temperature. At 24degree C, phentolamine did not alter the potentiation produced by (3H)POB, and reduced binding only slightly. There was no significant temperature differential in the amount of (3H)POB bound in the presence of phentolamine. 6. The results presented indicate a close functional and, probably, morphological association of alpha- and beta-adrenoceptors in the frog heart. It is suggested that the two classes of adrenoceptors may represent allosterie conformations of the same structure.

Animals↗
PubMed1976

Unmasking of sympathetic vasoconstruction of the coronary vessels after acute administration of reserpine to dogs.

Acute intravenous administration of reserpine or pretreatment of dogs with Segontin selectively abolished coronary vasodilation and unmasked a constrictor response to stimulation of the cardiac sympathetics. In view of earlier findings of separate coronary vasomotor and cardiostimulatory sympathetic innervation, the results are interpreted to indicate the existence of reserpine-resistant short (vasomotor) and reserpine-sensitive long (cardiostimulatory) sympathetic postganglionic neurons.

Animals↗
PubMed1974

Dissociation of 5-hydroxytryptamine effects on myocardial contractility and cyclic AMP accumulation.

1 5-Hydroxytryptamine increased the contractility of the isolated rat atrium and produced a small rise in cyclic 3',5'-adenosine monophosphate (cyclic AMP) accumulation in rat heart slices. These effects were similar to those of tyramine.2 Incubation with phenoxybenzamine prevented the inotropic effect of 5-hydroxytryptamine but did not inhibit the rise in cyclic AMP accumulation.3 A single injection of reserpine 24 h before the experiment did not inhibit the inotropic effect of 5-hydroxytryptamine but prevented the rise in cyclic AMP accumulation.4 It is concluded that in the rat 5-hydroxytryptamine increases cardiac contractility chiefly by a direct effect which is blocked by phenoxybenzamine, whereas it increases myocardial cyclic AMP accumulation indirectly by releasing endogenous catecholamines. Cardiac contractility may thus be increased without a rise in cyclic AMP accumulation, and cyclic AMP accumulation may be increased without a rise in contractility.

Adenine↗
PubMed1974

Dissociation of cardiac inotropic and adenylate cyclast activating adrenoceptors.

1 At higher temperatures, near the physiological range for mammals and nonhibernating frogs, the adrenoceptors for both inotropic responses to adrenaline and noradrenaline and for cyclic 3',5'-adenosine monophosphate (cyclic AMP) production in rat and frog isolated heart preparations, had typical beta characteristics. Phenoxybenzamine potentiated the inotropic response and the accumulation of cyclic AMP; conversely, propranolol inhibited the two responses.2 When the ambient temperature was reduced, the adrenoceptors mediating cyclic AMP production changed very little; they were blocked as effectively as at the higher temperature by propranolol and were not blocked by phenoxybenzamine. However, the adrenoceptors mediating the inotropic response were markedly changed by the decrease in temperature; phenoxybenzamine now inhibited this response and the inhibitory activity of propranolol was reduced about tenfold.3 These results indicate that the adrenoceptors that mediate cardiac inotropic responses at physiological temperatures are distinct from those that mediate the production of cyclic AMP, and that the activation of adenylate cyclase and the accumulation of cyclic AMP are probably not intermediate steps in cardiac inotropic responses to catecholamines.

Adenine↗