Biomedical subjects

J Bockaert

Publications and source records attributed to J Bockaert.

At least 253 records · Page 14Linked to original sources

PubMed1986

5-HT2 receptor-stimulated inositol phosphate formation in rat aortic myocytes.

Serotonin (5-HT) stimulated inositol phosphate production in primary cultures of rat aortic myocytes via a 5-HT2 receptor. Agonists active at 5-HT2 receptors in other systems were also active here but the response to some agonists was potentiated by the hormone uptake blocker, cocaine HCl. Two 5-HT2 selective antagonists, ketanserin and spiperone, inhibited the serotonin-induced response while compounds selective for other 5-HT receptor subtypes did not.

Animals↗

PubMed1986

Activation of phosphatidylinositol synthesis by different agonists in a primary culture of smooth muscle cells grown on collagen microcarriers.

Regulation of inositol phosphate synthesis was examined in a primary culture of vascular smooth muscle cells grown on collagen-coated microcarriers. In the presence of LiCl (10 mM), four agonists [serotonin, angiotensin, (arginine) vasopressin and noradrenaline] were found to stimulate the formation of inositol phosphates in a dose-dependent manner. All agonists were found to have identical and additive effects on the time course of inositol phosphate formation. Therefore, our primary cell culture technique was proved to give smooth muscle cells suitable for the study of modulation of phosphoinositide metabolism in response to physiological effectors.

Angiotensin II↗

PubMed1986

The binding of acidic amino acids to snail, Helix aspersa, periesophagic ring membranes reveals a single high-affinity glutamate/kainate site.

The characterization of specific acidic amino acid binding sites to snail, Helix aspersa, ganglia membranes has been assayed using tritiated glutamate (L-[3H]Glu), aspartate (L-[3H]Asp), cysteine sulfinate (L-[3H]CSA) and kainate. At 2 degrees C, only L-[3H]Glu and [3H]kainate specific binding could be measured using a filtration procedure to separate bound from free ligand. The analysis of L-[3H]Glu specific binding reveals the presence of one class of high-affinity binding sites with Kd = 0.12 microM and Bmax = 30 pmol/mg protein. This L-[3H]Glu binding was specific, reversible and saturable. The order of potency of different substances, agonists or antagonists of the rat brain excitatory amino acid receptors, has been determined. Kainate was the best displacing agent, followed by ibotenate = L-Glu greater than L-alpha-aminoadipate (L-alpha-AA) greater than homocysteate (HCA). Using 10 nM [3H]kainate, a single class of binding site was detected. Its pharmacological properties indicate that it is likely identical to the L-[3H]Glu binding site. This L-Glu-kainate site possesses most of the properties expected for a specific receptor. However, whereas L-[3H]Glu binding could be detected on purified neuronal membranes, the major component of specifically bound L-[3H]Glu appeared to be located on the sheaths surrounding neuronal cell bodies. These findings suggest that Glu or another endogenous acidic amino acid may function as a transmitter at neuromuscular junctions in Helix periesophagic ring, acting at a receptor distinct from those on nerve cells.

Amino Acids↗

PubMed1986

Serotonin 5-HT1 receptors mediate inhibition of cyclic AMP production in neurons.

In purified striatal and cortical neurons in primary culture, serotonin (5-HT) stimulated basal cyclic AMP production (EC50, 0.5 microM) 2.5- and 1.5-fold, respectively. The 5-HT1 selective agonists, RU 24969 and 8-hydroxy-2-(di-n-propylamino)tetralin (PAT), did not stimulate cyclic AMP production. However, 5-HT, RU 24969 and PAT inhibited VIP-stimulated cyclic AMP formation in a dose-dependent manner. The actions of selective agonists and antagonists at 5-HT receptors mediating attenuation of cyclic AMP production suggest that they may be of the 5-HT1 subtype.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed1986

Serotonin- and dopamine-sensitive adenylate cyclase in molluscan nervous system. Biochemical and electrophysiological analysis of the pharmacological properties and the GTP-dependence.

Helix aspersa neuronal cell membranes contain distinct serotonin (5-HT) and dopamine (DA) sensitive adenylate cyclases. We have taken advantage of the fact that in this system, both in vitro (enzymatic assays) and in vivo (electrophysiological measurements) experiments can be used to explore the GTP dependence and the pharmacological properties of this neurotransmitter-sensitive enzyme system. The first property was studied using non-hydrolysable GTP analogs (guanosine 5'-O-(3-thio-triphosphate) or GTP gamma S, and guanosine 5'-imido diphosphate or Gpp(NH)p). In vitro, these two components stimulate the enzyme activity but with different potencies (Kapparent = 10(-8) to 5 X 10(-8) M for GTP gamma S, and 10(-5) M for Gpp(NH)p). Intracellular injections of GTP gamma S, but not of Gpp(NH)p, produced an electrophysiological response similar to the one elicited by 5-HT and DA. These results imply that, even in the presence of the high endogenous GTP concentration normally present in the cell (10(-3) M), GTP gamma S may bind to the GTP-binding protein. Such an interpretation is consistent with the in vitro competition experiments between GTP and GTP gamma S for adenylate cyclase activation. The pharmacology of 5-HT and DA receptors involved in adenylate cyclase stimulation and electrophysiological responses was studied. Serotoninergic antagonists and neuroleptics inhibited the 5-HT-sensitive adenylate cyclase in a stereospecific manner. However, their inhibition was not simply competitive. Our results suggest that they irreversibly bind a component localized on the cytoplasmic side of the membrane. Unexpectedly, the DA receptor coupled with adenylate cyclase was insensitive to any of the several antagonists tested.

Adenylyl Cyclases↗

PubMed1986

Vasoactive intestinal peptide actions on cyclic AMP levels in cultured striatal neurons.

The actions of vasoactive intestinal peptide (VIP) on intracellular cyclic AMP, in primary cultures of striatal neurons, were examined. VIP stimulated cyclic AMP formation five-fold over basal levels in neurons after 6 days in vitro (DIV); half maximal activation (EC50) was obtained with 10 nM of the peptide. VIP stimulation was both more potent and effective than those due to adrenocorticotropin (ACTH), dopamine (DA) or serotonin (5-HT). VIP efficacy was augmented to 15-20-fold in the presence of 0.1 microM forskolin, which had virtually no effect on cyclic AMP production alone; VIP potency was unaffected. At saturating concentrations of VIP (0.1-1.0 microM), no other agonist can further activate cyclic AMP production. Under these conditions, the interaction with opiate, DA D2 and 5-HT1 receptors, whose activation results in the inhibition of cyclic AMP production, was shown. During the differentiation of striatal neurons, VIP stimulation of cyclic AMP over basal levels, in the presence of 0.1 microM forskolin, decreases progressively from 30-fold after 3 DIV to 11-fold after 10-13 DIV.

Animals↗

PubMed1986

Synaptogenesis of cultured striatal neurons in serum-free medium: a morphological and biochemical study.

Striatal neurons were cultured from the fetal mouse brain and maintained in serum-free medium for 14-21 days in vitro (DIV). Pretreatment of the culture dishes successively with a polycation followed by fetal calf serum resulted in rapid neuron attachment and neurite proliferation. After 9-10 DIV, electron microscope observations revealed the presence of vesicles in axon terminals forming mature synapses with axons and perikarya of adjacent neurons and in varicosities along extended axons. Synapsin I, a synaptic vesicle-specific protein, was present only in neuronal perikarya after 3 DIV, in perikarya and in varicosities along extended axons after 6 DIV, and in varicosities and contact points between axon terminals and adjacent axons or perikarya after 11-14 DIV. Neurotransmitter-stimulated intracellular formation of cAMP decreased markedly during neuronal differentiation. Inositol phosphate formation in response to neurotransmitters, however, increased significantly throughout the period of striatal neuronal development. K+ (56 mM) depolarization resulted in a 2-fold increase in endogenous gamma-aminobutyric acid (GABA) release from striatal neurons, 50% of which was Ca2+-dependent, between 3 and 11 DIV. Between 11 and 14 DIV, subsequent to synapse formation (as revealed by electron microscope observations), GABA release evoked by 56 mM K+ increased up to 5-fold, 75% of which was Ca2+-dependent. It appears that the complete differentiation of striatal neurons in serum-free medium may provide a suitable model for the study of the physiological and regulatory mechanisms involved in nerve cell development.

Animals↗

PubMed1986

Release of endogenous amino acids from striatal neurons in primary culture.

Endogenous amino acid release was examined in highly purified striatal neurons obtained from fetal mouse brain, and differentiated in primary culture. This study aimed to determine which amino acids are released from striatal neurons after a brief depolarization period induced by elevated potassium concentration or veratrine. Amino acids released into the extracellular medium, subsequent to a 3-min exposure of striatal neurons, were subjected to HPLC analysis. At 14 days in vitro potassium (56 mM) depolarization elicited a 25-fold increase in gamma-aminobutyric acid release, 85% of which was calcium-dependent. This effect was small but apparent at 7 days in vitro (two-fold increase) and greatly increased between 11 and 14 days in vitro, subsequent to the appearance of synaptic vesicles in nerve terminals. gamma-Aminobutyric acid release was readily reversible within minutes of return to the resting state. Veratrine induced a quantitatively similar but calcium-independent increase in gamma-aminobutyric acid release. Similar results were observed on aspartate and glutamate release, but the increase was very small even after 14 days in vitro (62.2 and 123.3% increase over basal release, respectively). Taurine and hypotaurine release increased during and after depolarization induced by potassium. This effect remained constant between 11 and 18 days in vitro. BAY K 8644, a dihydropyridine-sensitive calcium channel agonist, augmented the effect of 15 mM potassium on gamma-aminobutyric acid release, but this effect remained very small as compared to the potassium (56 mM) or veratrine effects. In addition, nifedipine inhibited this BAY K 8644-induced release. These results demonstrate the high level of differentiation among striatal neurons containing gamma-aminobutyric acid in this in vitro system.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1986

Primary culture of striatal neurons: a model of choice for pharmacological and biochemical studies of neurotransmitter receptors.

Striatal neurons were cultured from fetal mouse brain and maintained in serum-free medium for 14-21 days in vitro (DIV). A double coating of culture dishes with polyornithine and fetal calf serum was needed in order to obtain synaptic differentiation. Synaptic vesicles were present in axon terminals as well as in varicosities along extended axons. The presence of differentiated synapses was confirmed by the immunostaining of the preparation with synapsin I antibody. After 13 days in vitro synapsin I was present in axonal varicosities and particularly concentrated at contact points between axonal terminals and postsynaptic sites on adjacent axons or perikarya. On a surface of 429 mm2 on which 2211 cells were observed under phase contrast microscopy only 7% were stained with an antibody against GFAP (glial fibrillary acidic protein). One or two days after the formation of differentiated synapses (11 DIV), a Ca2+-dependent liberation of GABA was observed. These cultures are an excellent model for studying the coupling of some neurotransmitter receptors with an adenylate cyclase. In particular using this preparation we were able to demonstrate that dopamine (D2) and serotonin-(5-HT1) receptors are negatively coupled with an adenylate cyclase. These cultures are also an excellent model to study the coupling of some neurotransmitter receptors with inositol phosphate producing enzymes. We demonstrated for the first time that the quisqualate subtype of glutamate receptors is able to increase inositol phosphate production in striatal neurons.

Animals↗

PubMed1985

Pharmacological characterization of octopamine-sensitive adenylate cyclase in the flight muscle of Locusta migratoria L.

Octopamine stimulates (20-30-fold) the adenylate cyclase activity in a broken cell preparation of locust flight muscle. This stimulation is mediated by one receptor with an apparent affinity of 3.3 X 10(-6) M. The hydroxyl group in the para position on phenylethanolamine was absolutely necessary to obtain an agonist whereas the meta hydroxyl group or the presence of a catechol almost suppressed the activity. Similar pharmacological profiles were obtained on other locust muscles, i.e. mandibular and extensor tibiae muscles. The affinities of a large series of agonists and antagonists for the octopamine receptor coupled with an adenylate cyclase were compared to those reported for octopamine 1, 2A and 2B receptors based on physiological studies in the locust extensor tibiae muscle. It appears that the octopamine receptor coupled with adenylate cyclase is likely to be identical with the octopamine 2A receptor mediating the increase in the amplitude of slow motoneuron twitch tension. The results of the pharmacological experiments are discussed, in particular concerning the possible relationship between the octopamine receptor and alpha 1- and alpha 2-adrenoceptors.

Adenylyl Cyclases↗

PubMed1985

Forskolin-induced change of the size of adenylate cyclase.

Forskolin, a potent activator of cyclic AMP generating systems, has been proposed to act directly on the catalytic unit of adenylate cyclase. Nevertheless, some arguments indicate a possible role of the guanosine triphosphate-binding regulatory protein in forskolin action on adenylate cyclase. In this study, we have observed an increase in the apparent sedimentation coefficient of solubilized adenylate cyclase, elicited by forskolin, both in rat liver (from 6.4 +/- 0.1 to 7.2 +/- 0.1 S) and rat striatum (from 6.7 +/- 0.1 to 7.6 +/- 0.1 S). On both systems, a similar increase in the sedimentation coefficient was observed after preactivation of the enzyme with guanosine 5'-(beta, gamma-imido)triphosphate (Gpp(NH)p). In contrast to the Gpp(NH)p effect, the forskolin action was found to be reversible. Simultaneous pretreatments of adenylate cyclase with forskolin and Gpp(NH)p did not induce additive increases of the apparent sedimentation coefficient of adenylate cyclase. The modification of the size of solubilized adenylate cyclase was corroborated by gel filtration studies. In rat liver membranes, the Stokes radius of the solubilized enzyme increased from 59 +/- 1 A for basal state to 65 +/- 1 A for forskolin preactivated state. A possible explanation of our findings is that forskolin may stabilize the complex between the GTP-binding regulatory protein and the catalytic unit of adenylate cyclase in a reversible manner.

Adenylyl Cyclase Inhibitors↗

PubMed1985

Tissue expression and phylogenetic appearance of the beta and gamma subunits of GTP binding proteins.

Antibodies raised against the T-beta gamma dimer of bovine retinal transducin specifically bind to the beta and gamma subunits of transducin in calf retina. Tissues from different vertebrates, but not from invertebrates, contained a band comigrating with the beta subunit of transducin (T-beta) which was immunostained. This protein most likely corresponds to the beta subunit of GTP binding proteins of hormonal systems (G-beta). In non-retinal vertebrate membranes, the antibodies did not recognize the gamma subunits of G proteins whereas a band comigrating with bovine T-gamma was detected in frog or rat retina. Although T-beta was precipitated by the T-beta gamma antiserum, we failed to immunoprecipitate the G-beta from calf brain.

Animals↗

PubMed1985

Inhibition of hormonally regulated adenylate cyclase by the beta gamma subunit of transducin.

Transducin (T), the GTP-binding protein of the retina activates the cGMP phosphodiesterase system, and presents analogies with the proteins GS and Gi which respectively mediate adenylate cyclase activation and inhibition by hormone receptors. These proteins are all comprised of an alpha subunit carrying the GTP-binding site and a beta gamma subunit made of two peptides. The beta peptide (35 kd) appears similar in the three proteins. We demonstrate here that purified T beta gamma inhibits adenylate cyclase from human platelet membranes. This inhibition was observed when adenylate cyclase was stimulated by GTP, prostaglandin E1 (PGE1), NaF and forskolin, but not when stimulated by GTP(gamma)S. In the presence of GTP and forskolin, the T beta gamma-induced maximal inhibition was not additive with the alpha 2-receptor-induced adenylate cyclase inhibition mediated by Gi. Both inhibitions were suppressed at high Mg2+ concentrations, which as also known to dissociate T beta gamma from T alpha-GDP. This suggests that these adenylate cyclase inhibitions are due to the formation of inactive complexes of GS alpha-GDP with T beta gamma or Gi beta gamma. T beta gamma-induced inhibition did not require detergent and could be suppressed by simple washing. T beta gamma effects are dependent on its concentration rather than on its total amount. This suggests that T beta gamma can operate in solution with no integration into the membrane. Similar inhibitory effects of T beta gamma are observed on adenylate cyclase from anterior pituitary and lymphoma S49 cell lines.

Adenylyl Cyclase Inhibitors↗

PubMed1985

Irreversible blockade of beta-adrenergic receptors with a bromoacetyl derivative of pindolol.

A potent irreversible beta-adrenergic derivative of pindolol possessing a chemically reactive group (Br-AAM-pindolol) was synthesized. This compound devoid of agonist properties, competed for all (3H)-dihydroalprenolol (3H-DHA) binding sites in C6 glioma cell and rat cerebellum membranes. Pretreatment of C6 glioma cell membranes with Br-AAM-pindolol and subsequent washing resulted in a time- and dose-dependent blockade of beta-adrenergic receptors. A 50% blockade was achieved in the presence of 1.6 nM Br-AAM-pindolol. This blockade occurs specifically at the beta-adrenergic receptor level, as: 1) it induced a decrease of maximal isoproterenol stimulated adenylate cyclase activity with no modification of basal and sodium fluoride stimulated activity and 2) decreases of (3H)-DHA binding and stimulation of adenylate cyclase activity by the agonist were suppressed in the presence of isoproterenol, a beta-adrenergic agonist. Furthermore, Br-AAM-pindolol treatment did not affect (3H)-diazepam binding in C6 glioma cell membranes. Pretreatment of C6 glioma cells with Br-AAM-pindolol also reduced the response of adenylate cyclase to isoproterenol and the number of beta-adrenergic receptors. The blockade of beta-adrenergic receptors of C6 glioma cells by Br-AAM-pindolol was non-competitive, whereas the blockade obtained with AM-pindolol, a derivative of pindolol devoid of alkylating properties, was competitive. The irreversible blockade of beta-adrenergic receptors by Br-AAM-pindolol in rat erythrocyte membranes was substantiated by the demonstration that no recovery of beta-adrenergic receptors occurred during long term incubation of the membranes (48 h) following Br-AAM-pindolol treatment and subsequent washing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1985

Corticotropin-peptide regulation of intracellular cyclic AMP production in cortical neurons in primary culture.

Previous studies have provided evidence for adrenocorticotropic hormone (ACTH) effects on a wide variety of behaviors. However, the precise sites of action and the mechanisms by which these effects may be mediated have yet to be clearly elucidated. Although ACTH was shown to augment cyclic AMP levels in glial cells isolated from whole brain, other studies found little or no effect of ACTH peptides on cyclic nucleotide metabolism in slices of cerebral cortex or homogenates of whole brain. In the present study, our objective was to determine whether ACTH peptides regulate intracellular cyclic AMP levels in neurons of the cerebral cortex in primary culture. ACTH peptides stimulated cyclic AMP synthesis up to threefold in a dose-dependent manner; stimulation was complete within 5-10 min of exposure to agonists. Neurohormone efficacy was augmented by 0.1 microM forskolin (which was virtually ineffective alone); potency was unaffected. The order of potency (EC50) for increasing intracellular cyclic AMP levels was as follows: ACTH (1-24), ACTH (1-17) (10 nM) greater than alpha-melanocyte stimulating hormone, beta-melanocyte stimulating hormone (alpha-MSH, beta-MSH) (100 nM) greater than ACTH (1-10) (1 microM) greater than ACTH (4-10) (5 microM). The hexapeptide ACTH (4-9) as well as ACTH (11-24) were inactive at concentrations as high as 10 microM. Other neuropeptides derived from proopiocortin, such as beta-endorphin and Met- and Leu-enkephalin were without effect on basal or hormonally stimulated cyclic AMP synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1985

Pharmacological characterization of the angiotensin receptor negatively coupled with adenylate cyclase in rat anterior pituitary gland.

Angiotensin II (AII) inhibited anterior pituitary adenylate cyclase. Whereas GTP was necessary to fully express the AII inhibitory effect, Na+ was not required. The magnitude of inhibition (42 +/- 6%) permitted a pharmacological characterization of the AII receptor involved in adenylate cyclase inhibition. Angiotensin I (AI) was less potent than AII, and deletion of aminoacids in the N-terminal position resulted in a progressive reduction of the Ki (peptide concentration producing half-maximal inhibition). The Ki values were 3 +/- 0.9, 10, and 700 nM for AII, angiotensin III (AIII), and des-Asp, des-Arg-AII, respectively. Sarcosine in position 1 [( Sar, Phe]AII) increased the potency of inhibition (Ki = 0.12 +/- 0.12 nM). Different antagonists of the AII receptors appeared to be partial agonists. There was a very close correlation (r = 0.98) between the respective potencies of a series of AII analogs to inhibit adenylate cyclase and the potencies of these analogs to elicit PRL or ACTH release or to bind to AII-binding sites. Dopamine and AII inhibition of anterior pituitary adenylate cyclase were not additive. This suggests that both receptors are on the same cell and likely on lactotrophs. This hypothesis agrees with the observation that vasoactive intestinal peptide stimulation of adenylate cyclase was inhibited by AII, whereas corticotropin-releasing factor stimulation was unaffected. Although dopamine and AII inhibited the same adenylate cyclase, they had opposing effects on PRL release (inhibition and stimulation, respectively). The possible significance of this observation is related to a model implying that PRL release can be elicited through either a Ca+2 or a cAMP pathway.

Adenylyl Cyclase Inhibitors↗

PubMed1985

D2-dopamine receptor-mediated inhibition of cyclic AMP formation in striatal neurons in primary culture.

Dopamine (DA) regulation of intracellular cyclic AMP formation in purified, intact striatal neurons in primary culture was examined. DA (EC50, 3 microM) and vasoactive intestinal polypeptide (VIP; EC50, 10 nM) stimulated cyclic AMP formation by 2- and 5-fold, respectively. In the presence of 0.1 microM forskolin (which was virtually ineffective alone), neurohormone efficacy was augmented; potency was unaffected. In the presence of 0.1 microM SCH 23390, a selective D1 antagonist, the DA dose-response curve was shifted rightward in a competitive manner. At low concentrations (0.01-1.0 microM), however, DA inhibited basal cyclic AMP formation. The inhibitory effect, but not the shift of the dose-response curve, was blocked by 5 microM l-sulpiride, a selective D2 antagonist. At saturating concentrations of VIP (0.1-1.0 microM), no other neurohormone can further augment cyclic AMP formation. Under these conditions, increasing concentrations of DA resulted in a dose-dependent (IC50, 0.5 microM) inhibition of VIP-stimulated cyclic AMP synthesis. This effect was augmented in the presence of 0.1 microM SCH 23390 and blocked by 5 microM l-sulpiride. Sulpiride antagonism was stereospecific, with the l-isomer being 30-fold more potent than the d-isomer. The rank order of potency for a series of dopaminergic agonists and antagonists at the receptor mediating attenuation of cyclic AMP formation suggests that it is of the D2 type. Furthermore, both DA and Met-enkephalin inhibition of cyclic AMP formation is lost after exposure of striatal neurons to islet activator protein. These findings suggest that a D2 receptor mediates the inhibition of intracellular cyclic AMP formation by DA in striatal neurons in primary culture, and may do so by an interaction with the inhibitory guanine nucleotide regulatory protein of adenylate cyclase.

Adenylate Cyclase Toxin↗

PubMed1984

Direct and indirect effects of sulfhydryl blocking agents on agonist and antagonist binding to central alpha 1- and alpha 2-adrenoceptors.

The effects of p-chloromercuribenzoate and N-ethylmaleimide were evaluated on the binding of (3H)-p-aminoclonidine, (3H)-rauwolscine and (3H)-prazosin on rat brain alpha-adrenergic receptors. Pretreatment of the particulate fraction with increasing concentrations of p-chloromercuribenzoate indicated that the binding of all three radioligands was similarly inhibited with an IC50 of about 30 microM. This effect was then reduced when agonist [(-)-norepinephrine] or antagonist (phentolamine) were present during the pretreatment. Pretreatment of the particulate fraction at N-ethylmaleimide concentrations less than 100 microM specifically decreased the (3H)-p-aminoclonidine binding while binding of antagonist was unchanged. N-ethylmaleimide produced binding changes similar to those induced by GTP in control membranes, i.e. interconversion of the alpha 2-adrenoceptors states from a high affinity to a low affinity for agonists. Norepinephrine but not phentolamine reduced the effects of N-ethylmaleimide when present during the pretreatment. Taken together, these results suggest that the alpha 1- and alpha 2-adrenoceptors possess, within or close by the recognition site, an --SH group which can be blocked at low concentrations by p-chloromercuribenzoate but not by N-ethylmaleimide. In contrast, the group alkylated by the latter does not seem to be located in the recognition site domain but rather at a site important for the coupling between the alpha 2-receptor and the GTP-binding protein.

Adrenergic alpha-Agonists↗