Classification of calcium channels and the sites of action of drugs modifying channel function.
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Animals↗
Biomedical subjects
M Spedding
Publications and source records attributed to M Spedding.
Structure-affinity relationships of 12-sulfonyl derivatives of 5,8,8a,9,10,11,12,12a,13,13a-decahydro-6H-isoquino[2,1-g][1 ,6] naphthyridines at alpha-adrenoceptors.
Analogues of the potent alpha 2-adrenoceptor antagonist (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a- decahydro-3-methoxy-12-(methylsulfonyl)- 6H-isoquino[2,1-g][1,6]naphthyridine (1b) were prepared and evaluated for alpha 1- and alpha 2-adrenoceptor affinity. Affinity for alpha 2-adrenoceptors was assessed by displacement of [3H]yohimbine from rat cerebral cortical membranes and although 1b and close structural analogues demonstrated high affinity, none were selective for the alpha 2A or alpha 2B subtypes reputedly present in this tissue. All of the high affinity alpha 2-adrenoceptor ligands were, however, selective with respect to [3H]prazosin (alpha 1) binding. Affinity for [3H]yohimbine-labeled alpha 2-adrenoceptors was found to be highly dependent on the stereochemistry of the tetracyclic system. The 8a beta,12a alpha,13a alpha diastereomer of 1 (56) had moderate affinity for alpha 2-adrenoceptors while the 8a beta,12a beta,13a alpha diastereomer (55) had very low affinity. The affinity and selectivity of these agents for alpha 2-adrenoceptors was found to correspond to that observed for several isomeric yohimbine analogues which have similar relative and absolute stereochemistries. Deviation from the structure of 1 by opening the B ring, changing the position of the sulfonamide nitrogen, or changing the attachment of the D ring led to a dramatic decrease in alpha 2-adrenoceptor affinity. High binding affinity was found to correlate with functional antagonism in the guinea pig ileum. The reversal of clonidine-induced mydriasis in the rat was used to assess bioavailability and indicated that 1b was a potent alpha 2-adrenoceptor antagonist in vivo.
Adrenergic alpha-Antagonists↗
The guinea-pig ileum preparation as a model for 5-HT1A receptors: anomalous effects with RS-30199-193.
1. Agents that have high and selective affinity for the 5-HT1A site such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and N,N-dipropyl-5-carboxamidotryptamine (DP5CT) inhibited the responses to field stimulation in guinea-pig ileum preparations; the inhibitory effects were antagonized by methiothepin and spiperone, consistent with effects at the 5-HT1A site. 2. The inhibitory effects of DP5CT were pronounced in Tyrode solution containing low Ca2+ (0.9 mM), but were much less apparent in Tyrode solution containing 1.8 or 5.4 mM Ca2+. 3. Responses to DP5CT were abolished by pretreatment with phorbol dibutyrate (3 microM), whereas the responses to UK14304 were only slightly inhibited. 4. Buspirone and ipsapirone (1 microM) inhibited the responses to field stimulation, and the effects were resistant to idazoxan, but inhibited by 8-OH-DPAT or spiperone. 5. RS-30199-193 (5-chloro-2-methyl-1,2,3,4,8,9,10,10a-octahydronaphth-[1,8-cd]- aze pine hydrochloride) an azepine with high affinity for the 5-HT1A site in rat cerebral cortex in binding experiments, augmented contractions, but did not antagonize the responses to DP5CT or to 8-OH-DPAT. 6. The hybrid compound of RS-30199-193 with buspirone, RS-64459-193 (5-chloro-2-[4-(8-azaspiro[4,5]decane-7,9-dione)-but-1-yl]- 1,2,3,4,8,9,10,10a-octahydronaphth[1,8-cd]-3-azepine hydrochloride) maintained high affinity for the 5-HT1A binding site in rat brain and both inhibited the response to field stimulation and antagonized the responses to 8-OH-DPAT and DP5CT. Thus the buspirone side chain when added to RS-30199-193 appears either to induce affinity for a distinct subset of receptors in the guinea-pig ileum or is required for functional effectiveness at the 5-HTlA receptor.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Affinity of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines for alpha-adrenoceptors. Differential affinity of imidazolines for the [3H]idazoxan-labeled alpha 2-adrenoceptor vs the [3H]yohimbine-labeled site.
A series of 2-(tetrahydroisoquinolin-2-ylmethyl)- and 2-(isoindolin-2-ylmethyl)imidazolines were prepared and tested for alpha 1- and alpha 2-adrenoceptor affinity with radioligand binding. Several compounds, 5-fluoro-(5h), 5-chloro-(5j), 5,8-dimethoxy- (5r), and 5,8-dimethoxy- (5r),1-methyl- (5s) 2-(tetrahydroisoquinolin-2- ylmethyl)imidazoline, were found to be selective alpha 2-adrenoceptor ligands on the basis of displacement of [3H]yohimbine from rat cerebral cortical membranes. One compound, 2-[(8-chloro tetrahydroisoquinolin-2-yl)methyl]imidazoline (5m), showed a 36-fold difference in affinity for the [3H]idazoxan-labeled alpha 2-adrenoceptor relative to the [3H]yohimbine-labeled site, which may be evidence for alpha 2-adrenoceptor subtypes.
Animals↗
1,9-Alkano-bridged 2,3,4,5-tetrahydro-1H-3-benzazepines with affinity for the alpha 2-adrenoceptor and the 5-HT1A receptor.
A number of 1,9-alkano-bridged 2,3,4,5-tetrahydro-1H-3-benzazepines were prepared and evaluated for 5-HT1A receptor and alpha 2-adrenoceptor affinity by using radioligand receptor binding techniques. Several compounds displayed 5-HT1A receptor affinity comparable to, or greater than, the known 5-HT1A ligand buspirone. The highest affinity 5-HT1A receptor ligands were N-alkyl-, N-allyl-5-chloro-, and 5-methoxy-1,2,3,4,8,9,10,10a-octahydronaphth[1,8-cd]azapines (4c, 4m, 4n), which had pKi values of 7.9-8.1. The S enantiomer of 4c had a higher affinity for the 5-HT1A receptor than the corresponding R isomer (pKi of 8.2 for (S)-4c vs 7.7 for (R)-4c). These compounds had a relatively low affinity for the alpha 2-adrenoceptor (pKi of 7 or less). On the other hand, the closely related 5-chloro-2-methyl-2,3,4,8,9,9a-hexahydro-1H-indeno[1,7-cd]azepine (3b) had high affinity for both the alpha 2-adrenoceptor (pKi = 8.1) and 5-HT1A receptor (pKi = 7.6). These results indicate that the two receptors may share common recognition sites.
Animals↗
Pertussis toxin-sensitive G-protein activation does not influence the response to Bay K 8644 in embryonic chick myocytes.
Pretreatment of embryonic chick cardiac myocytes with pertussis toxin (1-2.5 micrograms ml-1 for 22 h) abolished the negative chronotropic effects of carbachol but not the positive inotropic effects of Bay K 8644. Neither guanosine 5'-O-3-thiotriphosphate (GTP gamma S 500 microM intracellularly), nor pertussis toxin (0.5-1 microgram ml-1 for 22 h) modified the agonist effects of Bay K 8644 on calcium channel currents recorded under whole-cell voltage clamp. These findings indicate that pertussis-sensitive guanine nucleotide binding (G)-proteins does not modulate the effects of calcium channel activators in embryonic chick cardiac myocytes.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Heterogeneity of alpha 2-adrenoceptors in rat cortex but not human platelets can be defined by 8-OH-DPAT, RU 24969 and methysergide.
1. Saturation experiments indicated that [3H]-yohimbine binding was specific, saturable and labelled a single population of sites in rat cerebral cortex (Kd 5.3 +/- 0.9 nM, Bmax 121 +/- 10 fmol mg-1 protein) and human platelets (Kd 0.7 +/- 0.1 nM, Bmax 152 +/- 10 fmol mg-1 protein). 2. The alpha 2-adrenoceptor antagonists, yohimbine, rauwolscine, WY 26703, idazoxan and BDF 6143 displaced [3H]-yohimbine binding to each tissue in a simple manner, with high affinity and Hill slopes close to unity. 3. The alpha 1-adrenoceptor agonist, oxymetazoline and the antagonist prazosin inhibited the binding of [3H]-yohimbine to rat in a complex manner consistent with an interaction at more than one site. However, indoramin and WB 4101 only appeared to interact with one site. In contrast, in human platelets, all antagonists gave rise to monophasic displacement curves with Hill slopes close to unity suggesting a single site of interaction. 4. The 5-hydroxytryptamine (5-HT) receptor ligands, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), RU 24969, and methysergide inhibited the binding of [3H]-yohimbine to rat cortex with high and low affinity, consistent with an interaction with two populations of binding sites. However, inhibition of [3H]-yohimbine binding to human platelets suggested a single site of interaction. The low affinity of 5-HT, 5-carboxyamidotryptamine (5-CT) and dipropyl-5-CT indicated that [3H]-yohimbine was not labelling a 5-HT1-like site in rat cortex. 5. The ability of 8-OH-DPAT, RU 24969 and methysergide in addition to prazosin and oxymetazoline to differentiate [3H]-yohimbine binding provides additional pharmacological evidence for heterogeneity within rat cortical alpha 2-adrenoceptors. However, if the two sites in rat cortex that are differentiated by the 5-HT ligands represent (alpha 2A- and alpha 2B-adrenoceptor subtypes as defined by prazosin and oxymetazoline, then they do not correspond to the population of sites in human platelets. As receptor classification should be linked to affinity of drugs rather than tissue distribution, the current classification of alpha 2-adrenoceptor subtypes does not appear to be satisfactory.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Alpha 2-adrenoceptor subtypes and imidazoline-like binding sites in the rat brain.
1. The binding of [3H]-yohimbine and [3H]-idazoxan to rat cortex and hippocampus is rapid, reversible and of high affinity. Saturation data indicate that a single population of binding sites exist for [3H]-yohimbine in the cortex (Bmax 121 +/- 10 fmol mg-1, protein; Kd 5.2 +/- 0.9 nM) and hippocampus (Bmax 72 +/- 6 fmol mg-1 protein; Kd 5.8 +/- 0.7 nM). [3H]-idazoxan labels one site in the cortex (Bmax 87 +/- 8 fmol mg-1 protein; Kd 4.1 +/- 0.9 nM) and hippocampus (Bmax 30 +/- 6 fmol mg-1 protein; Kd 3.5 +/- 0.5 nM), when 3 microM phentolamine is used to define non-specific binding. A second distinct [3H]-idazoxan binding site (Bmax 110 +/- 21 fmol mg-1 protein; Kd 3.6 +/- 0.07 nM) is identified in rat cortex if 0.3 microM cirazoline is used to define non-specific binding and 3 microM yohimbine is included to prevent binding to alpha 2-adrenoceptors. 2. Displacement studies indicate that the alpha 1-adrenoceptor antagonist prazosin and the 5-HT1 ligands 8-OH-DPAT, RU 24969 and methysergide differentiate [3H]-yohimbine binding into two components; a high and low affinity site. In contrast the displacement of [3H]-idazoxan by each ligand was monophasic. 3. The affinities of 8-OH-DPAT, RU 24969 and methysergide determined against [3H]-idazoxan binding to the cortex and hippocampus correlate significantly with the binding site displaying low affinity for prazosin and previously designated alpha 2A. In contrast, a poor correlation exists for the high affinity site for prazosin designated alpha 2B. 4. [3H]-idazoxan, in the presence of 3 microM yohimbine, labels a site that displays high affinity towards cirazoline, naphazoline and guanabenz, but low affinity towards clonidine, p-aminoclonidine, adrenaline, noradrenaline and the alpha 2-adrenoceptor antagonists yohimbine, rauwolscine, WY 26703 and BDF 6143. 5. The results of this study indicate that [3H]-yohimbine labels two sites; the alpha 2A- and alpha 2B-adrenoceptors whereas [3H]-idazoxan labels an alpha 2-adrenoceptor with a profile consistent with the alpha 2A-adrenoceptor subtype. In addition, [3H]-idazoxan labels an imidazoline binding site in the rat cortex that is pharmacologically distinct from alpha 2-adrenoceptors. The low affinity of clonidine and p-aminoclonidine indicates that the imidazoline-like binding site in rat cortex is different from the site labelled by [3H]-clonidine and [3H]-p-aminoclonidine in human, rat and bovine brain stem, providing evidence of potential heterogeneity within this class of binding sites.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
The influence of the initial stretch and the agonist-induced tone on the effect of basal and stimulated release of EDRF.
1. The effects of initial stretch and degree of agonist-induced tone on acetylcholine-induced relaxations were examined in rings of rat isolated aorta. The relaxation to acetylcholine was antagonized by atropine and almost completely abolished by haemoglobin. Relaxation to sodium nitroprusside was similar in rings with an intact or disrupted endothelium but that to isoprenaline was greater in intact preparations. 2. In preparations with either an intact or disrupted endothelium there was a similar length-dependent increase in the resting tension of the aortic rings. The size of the contractile response to phenylephrine (1 microM) was dependent on the initial length (and hence degree of stretch) of the preparation in both rubbed and unrubbed tissues. The absolute difference in contractile response between rubbed and unrubbed was greatest at 1.8 mm and less at the other lengths tested, including the optimum degree of stretch for contraction i.e. 2.4 mm. 3. The absolute acetylcholine-induced relaxation (only seen in rings with an intact endothelium) was dependent on the initial length (and hence degree of stretch) of the preparation and was maximum at 2.4 mm. The proportionate relaxation (i.e. expressed as a percentage of induced tone) was also length-dependent being optimal at 1.5 mm. 4. The sensitivity of the vessels to acetylcholine varied depending on the level of agonist-induced tone. When tone was low, acetylcholine sensitivity was high (at [NA] 0.03 microM: pIC50 = 7.36 +/- 0.07), when the concentration of noradrenaline was increased the tone increased and the acetylcholine sensitivity was low (at [NA] 0.3 microM: pIC50 = 6.57 +/- 0.07). 5. The absolute sensitivities and maximum relaxations induced by acetylcholine are discussed in relation to the initial degree of stretch (and hence length of the preparation) or the degree of agonist-induced tone.
Acetylcholine↗
Selective antagonism of calcium channel activators by fluspirilene.
1. Fluspirilene has been claimed to bind to a high affinity site in the calcium channel in skeletal muscle. We have investigated its calcium-antagonistic effects in smooth muscle and affinity for the channel in radioligand binding assays. 2. Fluspirilene was weakly active as an antagonist of Ca2(+)-induced contractions in K(+)-depolarized taenia preparations from the guinea-pig caecum, with threshold antagonism starting from concentrations of 30 nM. Nitrendipine, nicardipine and nimodipine were very potent antagonists in this model (threshold antagonism, greater than 1 nM). 3. In contrast, fluspirilene (10-1000 nM) was a potent non-competitive antagonist of the effects of Bay K 8644 (1-3000 nM) on Ca2(+)-induced contractions and, at 10 nM, selectively antagonised the effects of Bay K 8644, abolished the Ca2(+)-channel activator effects of CGP 28392, without changing the calcium antagonist effects of nitrendipine, or modifying the sensitivity of the tissues to Ca2+. In contrast, the dihydropyridines were more effective as antagonists of Ca2+ than of Bay K 8644. Fluspirilene therefore selectively antagonised the effects of dihydropyridine Ca2+ channel activators without affecting the antagonist potency. 4. In radioligand binding experiments, fluspirilene was a potent displacer of [3H]-PN-200-110 binding to rat cerebral cortical membranes (EC50 30 nM), albeit with a low Hill slope (0.66), and was more potent than other lipophilic diphenylalkylamines such as flunarizine and lidoflazine. Fluspirilene interacted non-competitively with [3H]-PN-200-110 and increased dissociation of the radioligand.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Interactions of palmitoyl carnitine with the endothelium in rat aorta.
1. Palmitoyl carnitine (10-1000 microM) resembled Bay K 8644 (10-1000 nM) in that it directly contracted rat aortic rings which were partially depolarized with K+ (12 mM). However, the effects of Bay K 8644 were reduced in the presence of endothelium whereas the presence of the endothelium hardly affected the palmitoyl carnitine-induced contractions, which occurred at high concentrations (greater than 10 microM). 2. Lower concentrations of palmitoyl carnitine (0.3-30 microM; EC50 1.1 microM), but not Bay K 8644, carnitine or palmitic acid, antagonized the relaxant effects of acetylcholine in rat aorta. The antagonism was specific for endothelium-dependent relaxations, in that the relaxations to ATP and the calcium ionophore A23187 were also non-competitively antagonized, albeit at slightly higher concentrations, whereas the direct relaxant effects of sodium nitroprusside were unaffected. Palmitoyl carnitine therefore antagonizes the effects or the release of endothelial-derived relaxant factor (EDRF). The inhibitory effects were reversed on prolonged washout, indicating that the effects were not due to destruction of the endothelial cells. 3. In superfusion experiments, palmitoyl carnitine inhibited the release of EDRF from rat aorta but did not affect the responsiveness to exogenous EDRF, indicating a site of action at the endothelial cell. In superfusion experiments, palmitoyl carnitine, and lysophosphatidyl choline, caused direct relaxations of the aorta, indicating EDRF release, prior to inhibition of release evoked by receptor stimulation. These substances may modulate vascular responsiveness under certain conditions.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Factors modifying the tissue selectivity of calcium-antagonists.
The factors modifying the tissue selectivity of calcium-antagonists are reviewed, with special reference to smooth muscle. Nicardipine was the most selective compound for the vasculature compared with the myocardium.
Animals↗
The alpha 2-adrenoceptor antagonist SK&F 104078 has high affinity for 5-HT1A and 5-HT2 receptors.
The affinity of SK&F 104078, a putative selective postjunctional alpha 2-adrenoceptor antagonist, was determined at 5-HT1A and 5-HT2 receptors in rat brain. SK&F 104078 had moderate affinity towards alpha 2-adrenoceptors (pKi 6.7) but displayed higher affinity at 5-HT1A (pKi 8.1) and 5-HT2 (pKi 7.6) receptors. If SK&F 104078 is used in functional studies to define heterogeneity within of alpha 2-adrenoceptors, care must be taken to define the role of 5-HT1A and 5-HT2 receptors in the response being measured.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
(8a alpha,12a alpha,13a alpha)-5,8,8a,9,10,11,12,12a,13,13a-decahydro- 3-methoxy-12-(methylsulfonyl)-6H-isoquino[2,1-g][1,6]naphthyridi ne, a potent and highly selective alpha 2-adrenoceptor antagonist.
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Adrenergic alpha-Antagonists↗
Activators and inactivators of calcium channels: effects in the central nervous system.
The interactions of calcium antagonists or channel activators with the different classes of calcium channel are reviewed with particular emphasis on interactions with neuronal tissue; reasons for the failure of calcium antagonists to inhibit neurotransmitter release under normal circumstances are outlined. Calcium antagonists may be protective in several pathological situations and the possibilities of protection against ischaemic damage in the central nervous system are evaluated.
Animals↗
The effects of calcium antagonists on calcium overload contractures in embryonic chick myocytes induced by ouabain and veratrine.
1. The protective effects of some calcium antagonists against different forms of calcium overload contracture were investigated in embryonic chick cardiac myocytes. 2. Tetrodotoxin-sensitive sodium currents were recorded from the myocytes by the whole-cell voltage-clamp technique. Although the peak current was attenuated by veratrine, the inactivation process was markedly inhibited, resulting in a large increase in the total inward current. Action potentials were prolonged by veratrine, automaticity was inhibited and the membrane potential depolarized from -79 to around -45 mV. 3. Measurements of contraction were made from aggregates of myocytes using a video edge detection technique which quantified edge movement. Veratrine caused an initial positive inotropism then inhibited automaticity of aggregates with subsequent development of a tonic contracture to around 300% of the twitch contraction. 4. Veratrine-induced contractures were not significantly affected by 10 microM diltiazem or verapamil. Nifedipine (5 microM), nimodipine (5 microM) and ryanodine (5 microM) also had little effect whilst nicardipine and flunarizine caused a concentration-dependent inhibition of veratrine-induced contractures with IC50s of 3 microM and 2 microM respectively. 5. Veratrine-induced contractures were found to be very sensitive to extracellular calcium concentration with an EC50 of 32 microM. Edge movement associated with beating of the myocytes was much less sensitive to calcium (EC50 = 1 mM). Submaximal veratrine contractures in 20-50 microM extracellular calcium were not potentiated by 1 microM Bay K 8644. 6. Tetrodotoxin also inhibited veratrine-induced contractures but did not affect contractions induced by ouabain in the presence of 10 microM diltiazem. 7. Ouabain-induced contractures were also inhibited by nicardipine and flunarizine indicating that these drugs can protect against calcium overload in embryonic chick heart by a mechanism independent of the normal form of voltage-sensitive sodium or calcium channels.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
Interaction of palmitoyl carnitine with calcium antagonists in myocytes.
1. Beating of aggregates of embryonic chick myocytes, in primary culture, was quantified by use of a motion-detector and video-recorder technique. Interactions of palmitoyl carnitine, a putative endogenous ligand at Ca2+ channels, with calcium antagonists were investigated. 2. Bay K 8644 (1-100 nM) and palmitoyl carnitine (0.2-30 microM) increased edge movement of the aggregates; beats fused so that there was an increase in baseline 'tone'. The concentrations required to produce a 50% increase in edge movement were 2.5 nM for Bay K 8644 and 2 microM for palmitoyl carnitine. Higher concentrations (20-30 microM) of palmitoyl carnitine caused tachycardia of abrupt onset but resulted in cessation of beating. The effects of palmitoyl carnitine were not stereo-selective in that the (+)- and (-)-isomers were equieffective. Lysophosphatidyl choline (LPC) had no effect in concentrations up to 10 microM but higher concentrations caused tachycardia followed by cessation of beating. High concentrations of both palmitoyl carnitine and LPC (100 microM) caused break-up of the aggregates, presumably as a result of detergent effects. 3. Palmitoyl carnitine (1-100 microM) reversed the inhibitory effects of nisoldipine (0.3 microM), diltiazem (10 microM) and verapamil (1 microM). Ouabain was ineffective in reversing the effects of nisoldipine, differentiating the effects of palmitoyl carnitine from those of Na+/K+ ATPase inhibition. In contrast, palmitoyl carnitine did not reverse the inhibitory effects of pimozide (2 microM) or lidoflazine (7 microM); palmitoyl carnitine showed a similar profile to Bay K 8644 in this respect. 4. These findings indicate that the effects of palmitoyl carnitine closely resemble those of Bay K 8644 and can be differentiated from those of lysophospholipids. As palmitoyl carnitine accumulates in the sarcolemma during myocardial ischaemia, the mode of action in the Ca2 + channel may have clinical relevance for the use of calcium antagonists in ischaemia.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
[3H]-idazoxan binds with high affinity to two sites on hamster adipocytes: an alpha 2-adrenoceptor and a non-adrenoceptor site.
1. [3H]-idazoxan labels a single population of high affinity sites (Kd 2.26 +/- 0.02 nM; Bmax 372 +/- 25 fmol mg-1 protein) in hamster adipocyte membranes. In the presence of 1 microM yohimbine to preclude binding to alpha 2-adrenoceptors, the density of [3H]-idazoxan binding sites was reduced (287 +/- 18 fmol mg-1 protein) without an apparent decrease in the affinity (Kd 2.19 +/- 0.24 nM) of the radioligand. 2. Displacement studies indicate that alpha-adrenoceptor ligands with an imidazoline side chain completely inhibit [3H]-idazoxan binding to hamster adipocyte membranes; in contrast, the alpha 2-adrenoceptor antagonists yohimbine, rauwolscine, BDF 6143 and phentolamine inhibited only 20-30% of the specific binding with affinity values consistent with an interaction at alpha 2-adrenoceptors. 3. The low potency of noradrenaline and adrenaline in displacing [3H]-idazoxan binding to the second site on hamster adipocyte membranes indicates that it is unlikely that this site is a type of adrenoceptor. 4. These results suggest that [3H]-idazoxan binds with high affinity to two sites in hamster adipocytes: an alpha 2-adrenoceptor and a non-adrenoceptor imidazoline site.
Adipose Tissue↗