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D Atlas

Publications and source records attributed to D Atlas.

At least 37 records · Page 2Linked to original sources
PubMed1994

Caffeine-induced transmitter release is mediated via ryanodine-sensitive channel.

An isolated clone PC12-37 of rat pheochromocytoma PC12 cells, which lacks ryanodine-sensitive Ca2+ channel, responds to depolarization and to agonist activation and triggers [3H]dopamine ([3H]DA) release. A caffeine-stimulated transmitter release, while present in the parental PC12 cell line, is completely abolished in PC12-37 cells. In contrast, caffeine-induced Ca2+ influx in PC12-37 cells is similar to that observed in PC12 cells, indicating that caffeine-induced CA2+ influx is neither mediated by caffeine-induced Ca2+ release nor contributes to the caffeine-induced secretion. These results show (a) a tight coupling between caffeine activation of a ryanodine-sensitive Ca2+ store and transmitter release, (b) no significant involvement of the ryanodine-sensitive Ca2+ channel in depolarization- and agonist-mediated transmitter release, and (c) exclude a major role for caffeine-mediated Ca2+ entry in the caffeine-activated secretion.

Animals↗
PubMed1993

A putative ATP-activated Na+ channel involved in sperm-induced fertilization.

Extracellular application of adenosine triphosphate (ATP) to defolliculated Xenopus laevis oocytes activated a saturating inward current with a maximal amplitude E(max) of 2.4 +/- 0.2 microamperes and an apparent Michaelis constant of 197.6 micromolar. The current was carried predominantly by sodium ions and potently inhibited by amiloride, guanosine triphosphate (GTP), and its nonhydrolyzable analogs guanosine 5'-[beta,gamma-imido]triphosphate (GppNHp) and guanosine 5'-O-(3-thiotriphosphate). Likewise, in vitro fertilization using mature eggs and Xenopus sperm was inhibited by amiloride, GTP, and GppNHp. Hence, an ATP receptor on the egg membrane may be the recipient target for ATP originating in sperm, suggesting that an ATP-induced increase in sodium permeability mediates the initial sperm to egg signal in the fertilization process.

Adenosine Triphosphate↗
PubMed1993

Detection and measurement of an endogenous clonidine-displacing substance in human cerebrospinal fluid.

Clonidine-displacing substance (CDS) is a novel endogenous ligand for clonidine receptors previously detected in bovine brain and human serum. We examined for the first time whether CDS can be detected and measured in human cerebrospinal fluid (CSF). Using the [3H]clonidine displacement assay, we found that CDS could be identified and quantified in each of the CSF samples obtained from 81 patients with various neurological disorders. Mean level of CDS in CSF was 4.66 units/ml. Exceedingly high levels were observed in the CSF of patients with neoplastic meningitis (mean, 36.75 units/ml) and stroke (mean, 19.5 units/ml) (P < 0.0001). No correlation was found between CDS levels in CSF and age, gender, CSF protein or number of cells. CDS levels in CSF were higher than those in the serum (P < 0.01). We conclude that CDS is present and can be measured in human CSF. High CDS levels in CSF from patients with leptomeningeal metastases may serve as a tumor marker for malignant infiltration of the meninges. Additional studies in stroke patients will determine whether this endogenous ligand plays a role in the pathogenesis of cerebral ischemia.

Adolescent↗
PubMed1993

Membrane depolarization combined with release of calcium from internal stores does not trigger secretion from PC 12 cells.

The mechanisms underlying catecholamine release from pheochromocytoma (PC 12) cells were examined. Whereas application of 1 microM bradykinin (BK) induced an increase in intracellular calcium ([Ca2+])i), either in medium containing 1.8 mM Ca2+ or in medium prepared without the addition of CaCl2 ("Ca(2+)-free medium"), norepinephrine ([3H]NE) release was induced only in Ca(2+)-containing medium. Similarly depolarization by 50 mM potassium induced [3H]NE release only in 1.8 mM calcium-containing medium. The combination of membrane depolarization (50 mM KCl) with increased [Ca2+]i secondary to BK application in "Ca(2+)-free medium" did not induce catecholamine secretion. It was concluded that Ca2+ entry through calcium channels at the plasma membrane is essential for the activation of catecholamine release. A rise in [Ca2+]i (4-5 times x basal) released from internal stores is not sufficient to trigger secretion from PC 12 cells, either by itself or in combination with membrane depolarization.

Animals↗
PubMed1992

Potency of depolarization-induced transmitter release is determined by divalent cation influx in PC 12 cells.

Evoked release of [3H]dopamine ([3H]DA) from pheochromocytoma cells (PC 12) is dependent on extracellular calcium ([Ca2+]ex), but it can take place if calcium ions (Ca2+) are substituted by other divalent ions such as strontium (Sr2+) and barium (Ba2+). The potency of the divalent cations at supporting release varies with the cell type; in PC 12 cells the order of potency is Ba2+ > Sr2+ > Ca2+. The close correlation between depolarization-evoked Ca2+ entry and depolarization-evoked transmitter release prompted us to examine whether the higher evoked transmitter release in the presence of Sr2+ correlates with an increased evoked Sr2+ influx. Influx studies were conducted on PC12 cells using a radioactive tracer (45Ca2+ or 85Sr2+, < 1 microM) in the presence of either Sr2+ (0.5 mM) or Ca2+ (0.5 mM). Depolarization with K Cl (60 mM) increased evoked 45Ca2+ influx 2-fold when Ca2+ was substituted with Sr2+. Similarly, evoked 85Sr2+ influx increased 1.87-fold by substituting Ca2+ for Sr2+. Thus the amount of evoked cation influx is determined by the type of divalent ion which is accessible in the extracellular medium, independently of the radioactive tracer used. Increased evoked transmitter release in the presence of Sr2+ was associated with increased evoked Sr2+ influx. This suggests that the potency of evoked transmitter release is determined predominantly by the influx of divalent cations. Furthermore, the steps subsequent to cation influx in the release process are equally efficient for both cations.

Animals↗
PubMed1992

Is imidazoline site a unique receptor? A correlation with clonidine-displacing substance activity.

Many specific hypotensive drugs acting via the central alpha 2-adrenoceptors were designed based on their imidazoline/guanidine structure for use as antihypertensives. This unique structure, which is missing in the alpha 2-adrenoceptor natural ligands, led to the search for an endogenous, nonadrenergic ligand, and later on, for its putative receptor. Indeed, an endogenous ligand designated the "clonidine displacing substance" (CDS), was isolated and purified from bovine brain, and characterized in various cells. The most intriguing feature of CDS is its hypertensive action upon injection into the rostral ventrolateral medulla and its competition with clonidine. Is CDS a natural agonist which is displaced by clonidine or other hypotensive drugs? Does the unique imidazoline/guanidine structure imply a unique recognition site? Recent studies reported that an imidazoline site, distinct from the alpha 2-adrenoceptor, is abundant in many tissues, and it preferentially recognizes the imidazolino-guanidino type ligands. The physiological role of these sites is still not well defined. In the present study we show that the richest tissue in imidazoline sites is human placenta (1800 +/- 100 fmol/mg protein). The sites are distributed on the cell surface, as observed in studies of binding to intact cytotrophoblasts and cultured trophoblasts originating from human placenta. Binding studies show that the imidazoline site displays a unique pharmacological profile distinct from the alpha 2-adrenoceptor (eg, benzylidenamino-guanidine, Ki = 18.9 +/- 13.8 nmol/L for the imidazoline sites and Ki = 768 +/- 299 nmol/L for the alpha 2-adrenoceptors; guanidopyrol, Ki = 11.2 +/- 6.3 nmol/L for imidazoline sites and Ki = 10100 +/- 1515 nmol/L for the alpha 2-adrenoceptors).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Imidazoline binding sites in human placenta: evidence for heterogeneity and a search for physiological function.

1. An alpha 2-adrenoceptor antagonist, idazoxan, that binds to both alpha 2-adrenoceptors and to imidazoline sites (IR), has been used to characterize human placental IR. Human placenta is shown to be the richest source of IR (1800 +/- 100 fmol mg-1 protein; Kd 38.9 +/- 3.4 nM). 2. Primary cells derived from human placenta and grown in monolayers, also displayed a high density of receptors (3209 +/- 136 fmol mg-1 in cytotrophoblasts and 3642 +/- 144 fmol mg-1 protein in syncytiotrophoblast enriched cell culture). 3. [3H]-idazoxan did not show binding characteristics of alpha 2-adrenoceptors in human placental membranes or human trophoblastic cells, thus making it a ligand of choice to study the imidazoline site. The tissue appeared to be lacking alpha 2-adrenoceptors in that other alpha 2-adrenoceptor ligands, [3H]-rauwolscine and [3H]-clonidine, do not bind to alpha 2-adrenoceptors in human placenta. 4. IRs are localized on the cell surface, as determined by the release of bound [3H]-idazoxan from cells, when washed with high ionic/acidic medium. 5. Imidazoline receptors of human placenta display high affinity for amiloride (72 +/- 27 nM). The high affinity was used as a criterion to classify IR to IRa subtype (placenta, rabbit kidney, rabbit liver and rabbit adipose cells) as opposed to the IRb subtype which display low affinity for amiloride (greater than 2 microM, in all the other tissues).6. Several novel ligands comprising a guanido functional group attached to an aromatic residue (e.g. benziliden-amino-guanidine (BAG), guanido pyrole) display pronounced selectivity for IR over the M2-adrenoceptors as the affinity of BAG is about 40 fold higher (Kd= 18.9 +/- 13.8 nM in human placenta), than the affinity for M2-adrenoceptors (Kd = 768 +/- 299 nM in human platelets). Imidazoline sites bind selectively BAG and other guanido ligands thus indicating a distinct structural requirement at its site of binding.7. K+ channel blockers and monovalent ions (e.g. Cs' and NH4+) interfere with idazoxan binding to IR, indicating a possible involvement of IR in K+ transport.

4-Aminopyridine↗
PubMed1991

ATP receptor. A putative receptor-operated channel in PC-12 cells.

External ATP induces [3H] dopamine [( 3H]DA) release in rat pheochromocytoma cells (PC-12 cells). The ATP-induced release is a saturable process with half-effective concentration of EC50 = 80 microM. ADP is a poor secretagogue of [3H]DA (one-sixth of ATP) and AMP is devoid of secretory capabilities. Adenosine and the non-hydrolyzable analogues of ATP, AppNHp and AppCp are ineffective as inducers of [3H]DA, release, or as inhibitors of the ATP-induced [3H]DA release. The most potent antagonist of ATP-induced release is Coomassie Blue (IC50 = 25 microM), compared to ADP beta S (IC50 = 500 microM). The overall rank order of potency is ATP greater than ADP much greater than AMP greater than adenosine, which is characteristic of the P2-purinergic receptor. ATP-induced secretion is absolutely Ca2+ dependent, indicating an exocytotic process and is independent of Mg2+ (up to 2 mM) suggesting that the active species is not ATP4-. (a) The ATP-induced 45Ca2+ influx into the cells is in good correlation to ATP induction of release (IC50 = 80 and 90 microM, respectively) and is carried over to ADP which has a diminished ability to induce both release and 45Ca2+ influx. (b) Divalent cations (Ba2+ greater than Sr2+ greater than Ln3+ greater than Mn2+) replace Ca2+ and support ATP-induced release similar to their effectiveness in supporting bradykinin- and K+ (50 mM)-induced release in PC-12 cells (Weiss, C., Sela, D., and Atlas, D. (1990) Neurosci. Lett. 119, 241-245). Combined together the absolute requirement of [Ca2+]ex for release, inhibition of release by Gd3+ (IC50 = 100 microM), Ni2+, and Co2+ (IC50 = 1 mM), and support of release by Ba2+, Sr2+, and Mn2+, we suggest that ATP induces Ca2+ entry via ligand-operated Ca2+ channels as previously suggested for ATP in smooth muscle cells (Benham, C.D., Bolton, T.B., Byren, N.G., and Large, W.A. (1987) J. Physiol. (Lond.) 387, 473-488). No significant inhibition by 1 microM verapamil, 10 microM nifedipine, or 2 mM Cd2+ argues against ATP activation of voltage-dependent Ca2+ channels as similarly shown for ATP-induced [3H]noradrenaline release (Inoue, K., Nakazawa, K., Fujimoro, K., and Takanaka, A. (1989) Neurosci. Lett. 106, 294-299). Thus, the widely distributed ATP receptor might play an essential role in Ca2+ homeostasis of the cell by introducing Ca2+ into the cell via specific ligand-gated Ca2+ channels.

Animals↗
PubMed1991

The bradykinin receptor--a putative receptor-operated channel in PC12 cells: studies of neurotransmitter release and inositol phosphate accumulation.

Bradykinin (BK) induced [3H]norepinephrine [( 3H]NE) release and phosphatidylinositol turnover were investigated in PC12 cells. Induction of [3H]NE release by BK is mediated by activation of BK-B2-receptors, as determined using type specific BK receptor antagonists. BK induces [3H]NE release with a half maximal effective concentration of 30 +/- 0.5 nM, and reaches maximal net fractional release of 9.0 +/- 1% with 200 nM BK. The BK-induced release is Ca2+ dependent, reaching maximal release at 1.0 mM Ca2+, is pertussis toxin insensitive (1 microgram/ml), slightly increased by a dibutyryl cAMP (1 mM) and not affected by inhibitors of the cyclooxygenase or lipoxygenase pathways. Voltage-sensitive Ca2+ channel blockers, verapamil (10 microM), nifedipine (10 microM), and omega-conotoxin (CgTx 10 nM), do not block the BK-induced release. However, a considerable inhibitory effect was obtained by divalent cations Co2+ (ED50 = 0.2 mM) and Ni2+ (ED50(2)+ = 1 mM). These results indicate the involvement of a Ca2+ channel in the BK-mediated release which is different from the L- or N-type voltage sensitive calcium channels. Whereas [Ca2+]ex is essential for the BK-induction of catecholamine release, the rise in level of InsP's induced by BK in the presence or in the absence of [Ca2+]ex is similar up to concentration of 1 microM. This indicates that the rise in InsP's induced by BK is not sufficient to cause neurotransmitter release. Moreover, subsequent addition of Ca2+ to BK-stimulated cells in Ca(2+)-free medium yields no release. Hence, no activity triggered by BK alone could be further stimulated by Ca2+ for induction of release.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1991

Human plasma-derived material with clonidine displacing substance (CDS)-like properties contracts the isolated rat aorta.

1. The biological activity of a plasma-derived, clonidine displacing substance (CDS)-like material was tested on isolated rat aortic rings and compared to that of clonidine, an imidazoline with alpha 2-adrenoceptor agonist properties. 2. The CDS-like material was partially purified from expired human blood. This product inhibited in a dose-dependent manner the binding of [3H]-clonidine to rat brain membranes with a ki of 0.87 +/- 0.4 u ml-1, without affecting the binding of the alpha 1-antagonist, [3H]-WB4101. 3. When the CDS-like material (0.14-6 u ml-1) was applied to the bathing medium of isolated rat aortic rings, it caused dose-dependent contractions with an EC50 of 1.0 +/- 0.18 u ml-1. Clonidine also dose-dependently contracted rat aortic rings (EC50, 1.1 +/- 0.24 x 10(-7) M). The maximal tension developed in response to clonidine, however, was higher (1.37 +/- 0.15 g) compared to that developed in response to the CDS-like material (0.92 +/- 0.12 g). 4. Contractions induced by both CDS-like material and clonidine were antagonized by 5 x 10(-7) M rauwolscine, an alpha 2-adrenoceptor antagonist. Prazosin, an alpha 1-adrenoceptor antagonist, at 10(-8) M, greatly reduced contractions caused by clonidine while leaving those caused by CDS-like material unaffected. 5. The CDS-like material failed to alter the tension of intact or endothelium-denuded rat aortic rings which had been precontracted with methoxamine. Clonidine on the other hand, caused dose-dependent relaxations in intact, though not in denuded, precontracted rat aortic rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1990

Divalent cations effectively replace Ca2+ and support bradykinin induced noradrenaline release.

Bradykinin (BK), a nonapeptide acting at the B2-type BK-receptor, and depolarization with high KCl (50 mM), induce catecholamine secretion in pheochromocytoma cells (PC-12). The mechanism underlying the BK-induced release, which is absolutely Ca2(+)-dependent, is not yet understood. Alkaline metals, barium (Ba2+), strontium (Sr2+) and other metal cations, manganese (Mn2+) or lanthanum (La3+), support BK-induced [3H]noradrenaline ([3H]NA) release. The extent of supporting transmitter release is dependent upon the specificity of the extracellular cation, with rank order potency of: Ba2+ greater than Sr2+ greater than Ca2+ greater than Mn2+La3+. The same rank order potency was observed for supporting both BK- and K(+)-induced release. [3H]NA release in the presence of Ba2+ or Sr2+ was much greater than in the presence of Ca2+, and unlike with Ca2+ was not saturable at the highest concentration measured. La3+ and Mn2+ were significantly less effective than Ca2+ at supporting release. These results strongly suggest that extracellular Ca2+ entry is essential for release, and that BK mediates release via a receptor-operated Ca2+ channel.

Adrenal Gland Neoplasms↗
PubMed1990

Imidazoline receptors in rat liver cells: a novel receptor or a subtype of alpha 2-adrenoceptors?

An imidazoline/guanidine receptor has been characterized in rat liver cells. Binding of [3H]idazoxan, a selective benzodioxan antagonist, to imidazoline receptor on intact fresh hepatocytes (Bmax = 801 +/- 23 fmol/mg protein, Kd = 11 +/- 0.8 nM) and to liver membranes (Bmax = 400 +/- 38 fmol/mg protein, Kd = 10 +/- 2 nM) was saturable at 4 degrees C within 3.5 h and at 30 degrees C within 30 min, respectively. Rat lung membranes had more imidazoline sites (Bmax = 578 +/- 30 fmol/mg protein, Kd = 14 +/- 1.4 nM) than alpha 2-adrenoceptors (Bmax = 175.0 +/- 20.0 fmol/mg protein, Kd = 4.8 +/- 2.0 nM). We also screened other tissues for imidazoline sites; the ratio of adrenoceptors to total sites labeled with [3H]idazoxan displaced by cirazoline was lower in rat lung compared to rat brain and human platelets. The imidazoline receptor has common pharmacological properties with alpha 2-adrenoceptors, although it is not a subtype of the adrenoceptor, since it bound neither the endogenous agonists norepinephrine and epinephrine, nor the selective alpha 2-antagonists yohimbine and phentolamine. All guanidine type alpha 2-adrenoceptor drugs (e.g. guanbenz, guanoxan) and imidazolines (e.g., UK-14,304, naphazoline) competed with high affinity for the liver imidazoline receptor. The lack of effect by Gpp(NH)p, a non-hydrolysable GTP analogue, on the affinity of guanidine- and imidazoline-type ligands for liver imidazoline receptors suggests that the mode of action of these drugs at imidazoline receptors is different than at conventional alpha 2-adrenoceptors. Ionic changes were considered as a possible mechanism underlying the alpha 2-adrenoceptor effects in various cells. Opening of K+ channels by alpha 2-adrenoceptors agonists is a pathway which might be shared by imidazoline-type agonists at imidazoline sites. Indeed, 4-aminopyridine, a K+ channel blocker, inhibited the specific binding of [3H]idazoxan to liver cells with an IC50 of 0.34 +/- 0.07 mM a concentration which is effective in blocking K+ channels in neuronal cells. Similarly, Cs+ and NH4+ effectively interfered with [3H]idazoxan binding, suggesting a possible coupling of imidazoline sites to K+ gating. The endogenous ligand clonidine-displacing substance (CDS), which was isolated from bovine brain and which binds to alpha 2-adrenoceptors in brain membranes and human platelets competed with idazoxan at rat liver imidazoline receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-Agonists↗
PubMed1990

Potentiation of neurotransmitter release coincides with potentiation of phosphatidyl inositol turnover. A possible in vitro model for long term potentiation.

Carbachol (CCh) a cholinergic agonist which hydrolyses phosphatidyl-inositol bisphosphate (PIP2) to produce the breakdown products inositol trisphosphate (IP3) and diacylglycerol (DAG) was tested for its ability to induce [3H]norepinephrine ([3H]NE) release and to accumulate [3H]inositol phosphate ([3H]IP) under normal and membrane depolarizing conditions. Our results suggest two major points: first, muscarinic acetylcholine receptor (mAChR) agonists and depolarizing agents (of which KCl is the most effective) act in concert to induce potentiation of PI turnover and potentiation of neurotransmitter release. The simultaneous presence of both a depolarizing agent and a receptor agonist is obligatory for eliciting potentiatory effect. Facilitation of release by muscarinic agonist and K+, added together, was 2 to 5-fold above additivity and the levels of [3H]IP accumulated were 3-5-fold above additivity by K+ and CCh. Enhancement of release and of [3H]IP formation is reversed by pirenzepine, a muscarinic (MI) specific antagonist, Kdiss = 0.4 and 0.8 microM, respectively. Second, synergy of IP accumulation in correlation with synergy of neurotransmitter release elicited by mAChR activation and membrane depolarization, suggests a possible role for phospholipase C (PLC) in the bifurcating control of neurotransmitter release and for the involvement of PLC and voltage sensitive channels in mediation of long-term potentiation (LTP).

Animals↗
PubMed1990

Imidazoline-guanidinium receptive site in renal proximal tubule: asymmetric distribution, regulation by cations and interaction with an endogenous clonidine displacing substance.

In the present report we have used [3H]idazoxan to characterize the rabbit renal imidazoline preferring site by defining its plasmalemma distribution, its regulation by cations and the type of interaction with the clonidine displacing substance (CDS), a putative endogenous ligand for the imidazoline receptor. The density of [3H]idazoxan binding sites was 12-fold higher in purified basolateral membranes than in brush-border membranes (maximal binding activity, 566 +/- 118 vs. 46 +/- 2 fmol/mg of protein). In basolateral membranes, [3H]idazoxan binding was inhibited not only by imidazoline compounds but also by guanidinium analogs such as guanabenz, amiloride, 5-(M-ethyl-N-isopropyl)amiloride and phenamylamiloride. Amiloride had no effect on the dissociation rate of [3H]idazoxan, suggesting a direct interaction of this molecule with the ligand binding site. [3H]Idazoxan binding was 80% inhibited by 150 mM K+ or Rb+. The effect of K+ appeared to occur through the interaction with an allosteric site in as much as both the apparent dissociation constant and the dissociation rate of [3H]idazoxan were increased in the presence of 75 mM K+. CDS inhibited [3H]idazoxan binding with a half-maximal effective concentration of 2 U/250 microliters. The competitive nature of CDS effect was indicated by the increase in the apparent dissociation constant of [3H]idazoxan (Kd from 3 +/- 0.3 to 8.5 +/- 0.2 nM, P less than .01) in the presence of CDS. In conclusion, our findings showed that the imidazoline-guanidinium receptive site is located mainly in the basolateral side of the tubular cell, recognizes CDS and is regulated by K+.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1989

Potentiation of [3H]inositol phosphate formation by receptor activation and membrane depolarization in brain cortical slices (I).

Potentiation of [3H]inositol phosphate ([3H]IP) accumulation by receptor agonists combined with depolarizing agents was studied in rat brain cortical slices, prelabeled with [3H]inositol. Muscarinic agonists, alpha 1-adrenergic, histaminergic and serotonergic agonists remarkably enhanced (2-7-fold) the accumulation of [3H]IP in the presence of KCl (30 mM). The potentiated levels of [3H]IP were strongly dependent on K+ concentration and displayed a dose-response relationship with the agonist. Other depolarizing agents such as veratridine and ouabain induce potentiation of [3H]IP formation similarly to that observed by KCl, but to a lesser extent. The production of elevated levels of [3H]IP is Ca2+-dependent with maximal effect at 0.6 mM which is similar to the Ca2+ dependency observed for the agonist and the depolarizing agent alone. Enhanced [3H]IP levels induced by agonists in the presence of depolarizing agents affect Vmax values only, since the apparent half maximal effective concentration of carbachol (CCh)-induced-IP-formation (1.2 x 10(-4) M) and of the phenylephrine-induced IP-formation (8 x 10(-6) M), were not affected in the presence of either K+ or veratridine. In addition the efficacy of various muscarinic agonists as inducers of IP-accumulation was conserved under depolarizing conditions as compared to IP accumulation under normal conditions. In the presence of KCl (30 mM) the maximal degree of potentiation was at a range of 5-7-fold, with order efficacy of ACh greater than CCh greater than Oxo M greater than arecoline much greater than pilocarpine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗