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J Jakway

Publications and source records attributed to J Jakway.

9 recordsLinked to original sources
PubMed2003

Pharmacological characterization of alpha 2-adrenoceptor-mediated responses in pig nasal mucosa.

1. Pig nasal mucosal strips were incubated with alpha-adrenoceptor antagonists followed by alpha2-adrenoceptor agonist concentration-response curves. 2. Contractions elicited by the alpha2-adrenoceptor agonists BHT-920 (pD2 = 6.16 +/- 0.07), UK 14,304 (pD2 = 6.89 +/- 0.13) and PGE-6201204 (pD2 = 7.12 +/- 0.21) were blocked by the alpha2-adrenoceptor antagonist yohimbine (0.1 microm). In contrast, the alpha1-adrenoceptor antagonist prazosin (0.03 microm) had no effect on the BHT-920-, UK 14,304- and PGE-6201204-induced contractions, but blocked the contractile response to the alpha(1)-adrenoceptor agonist phenylephrine (pD2 = 5.38 +/- 0.04) and the mixed alpha1- and alpha2-adrenoceptor agonist oxymetazoline (pD(2) = 6.30 +/- 0.22). 3. The alpha2-adrenoceptor antagonist yohimbine (0.01-0.1 microm, pA2 = 8.04), alpha2B/C-adrenoceptor antagonist ARC 239 (10 microm, pK(b) = 6.33 +/- 0.21), alpha2A/C-adrenoceptor antagonist WB 4101 (0.3 microm, pK(b) = 8.01 +/- 0.24), alpha2A-adrenoceptor antagonists BRL44408 (0.1 microm, pK(b) = 6.82 +/- 0.34) and RX 821002 (0.1 microm, pKb = 8.31 +/- 0.35), alpha2C-adrenoceptor antagonists spiroxatrine (1 microm, pKb = 7.32 +/- 0.32), rauwolscine (0.1 microm, pKb = 8.16 +/- 0.14) and HV 723 (0.3 microm, pKb = 7.68 +/- 0.14) inhibited BHT-920-induced contractions in pig nasal mucosa. 4. The present antagonist potencies showed correlations with binding affinity estimates (pKi) obtained for these antagonists at the human recombinant alpha2A- and alpha2C-adrenoceptors (r = 0.78 and 0.83, respectively) and with binding affinity estimates (pKd) obtained in pig native alpha2A- and alpha2C-monoreceptor assays (r = 0.85 and 0.78, respectively). No correlation was observed for the alpha2B-subtype. 5. In conclusion, contractile responses to phenylephrine, BHT-920, UK 14,304, PGE-6201204 and oxymetazoline indicate that alpha1- and alpha2-adrenoceptors are present and mediate vasoconstriction in pig nasal mucosa. Furthermore, correlation analysis comparing antagonist potency in pig nasal mucosa with affinities for human recombinant alpha2-adrenoceptors and native pig alpha2-adrenoceptors suggest that alpha2A- and alpha2C-adrenoceptor subtypes constrict pig nasal mucosa vasculature.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2001

Postjunctional alpha(2C)-adrenoceptor contractility in human saphenous vein.

The postjunctional alpha(2)-adrenoceptor-mediated contractility was characterized in human saphenous vein derived from coronary artery bypass graft surgery. Human saphenous vein contracted to alpha(2)-adrenoceptor selective agonists BHT-920 (5,6,7,8-Tetrahydro-6-(2-propenyl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride; pD(2)=6.7+/-0.1) and UK 14,304 (5-Bromo-6-(2-imidazolin-2-ylamino)quinoxaline; pD(2)=7.2+/-0.1). BHT-920-induced contractions were inhibited by the alpha(2)-adrenoceptor antagonist yohimbine (17-Hydroxy-yohimban-16-carboxylic acid methyl ester hydrochloride; pA(2)=8.7+/-0.5), but not by the alpha(1)-adrenoceptor antagonist prazosin (1-[4-Amino-6,7-dimethoxy-2-quinazolinyl]-4-[2-furanylcarbonyl]-piperazine hydrochloride; 300 nM). In contrast, prazosin (pK(b)=7.9+/-0.2) potently antagonized contractions elicited by the alpha(1)-adrenoceptor agonist phenylephrine ((R)-3-Hydroxy-alpha-[(methylamino)methyl] benzenemethanol hydrochloride; pD(2)=4.9+/-0.1), indicating that both alpha(2)- and alpha(1)-adrenoceptor evoke human saphenous vein contractions. Functional antagonist activity estimates (pA(2) or pK(b)) obtained for the alpha-adrenoceptor antagonists ARC 239 (2-[2-(4-(2-Methoxyphenyl)piperazin-1-yl)ethyl]-4,4-dimethyl-1,3-(2H,4H)-isoquinolindione dihydrochloride), WB 4101 (2-(2,6-Dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane hydrochloride) and HV 723 (alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy) ethyl)amino)propyl)benzeneacetonitrile) against BHT-920-induced human saphenous vein contractions were 7.0+/-0.6, 8.3+/-0.6 and 7.7+/-0.3, respectively. The alpha(2)-adrenoceptor subtype affinities (pK(i)) obtained in recombinant human alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptor competition binding assays were 8.6, 8.3 and 8.6 for yohimbine; 6.3, 8.4 and 7.0 for ARC 239; 8.4, 7.5 and 8.4 for WB 4101 and 7.5, 7.4 and 7.9 for HV 723, respectively. Taken together, the binding and functional antagonist activity estimates obtained in these investigations indicate that alpha(2C)-adrenoceptor is the predominant postjunctional alpha(2)-adrenoceptor subtype in human saphenous vein.

Adrenergic alpha-Agonists↗
PubMed2000

Receptor reserve analysis of the human CCR3 receptor in eosinophils and CCR3-transfected cells.

A novel pharmacological study of CCR3 receptor reserve in a CCR3-transfected cell (CREM3) and human eosinophils was done; functional responses measured were increases in intracellular calcium and chemotaxis. Eotaxin, eotaxin-2, monocyte chemoattractant protein-4 (MCP-4), RANTES, and MCP-3 induced similar maximal eosinophil chemotaxis, whereas MCP-3 and RANTES induced submaximal calcium responses in eosinophils compared to eotaxin, MCP-4, and eotaxin-2. This suggested a receptor reserve in the chemotaxis response. Receptor reserve was quantitated for eotaxin. Occupancy of all CCR3 receptors was required for a maximal calcium response in both CREM3 and eosinophils (reserve = 1.0 or 0.17, respectively); the stimulus-calcium response relationship was linear, indicating no receptor reserve. In contrast, in eosinophils a large receptor reserve (6.5) was found for chemotaxis, where occupancy of 15% receptors drove half-maximal responses. These studies indicate that CCR3 interacts with G-proteins that are poorly coupled to the calcium response, whereas coupling efficiency and/or amplification to the chemotaxis apparatus in human eosinophils is significantly greater.

Animals↗
PubMed1993

Column agglutination technology: the antiglobulin test.

A new system for typing and screening blood, based on the sieving effect of glass bead microparticles, has been developed. The test is performed in a microcolumn in which the red cell agglutinates are trapped in the glass bead matrix during centrifugation, and unagglutinated cells form a pellet at the bottom of the column. Anti-human globulin reagents were incorporated in the diluent and the new test system, column agglutination technology, was compared to conventional tube tests and low-ionic-strength method. Sera and plasmas (228 samples) were screened for red cell antibodies with two anti-human globulin reagents: one containing only anti-IgG and the other containing both anti-IgG and anti-C3b, -C3d. After initial testing, there was 94-percent agreement between column agglutination technology and tube tests, and after repeat testing, there was 97-percent agreement. The column agglutination technology anti-human globulin test eliminates the need to wash red cells, which decreases the overall test time. The test is easy to perform, and the results are more objective than those with tube and microplate methods.

Antibodies, Anti-Idiotypic↗
PubMed1993

Cost considerations in therapy with myeloid growth factors.

Costs of biologic response modifiers, specifically myeloid growth factors, are discussed relative to cost offsets they may produce in the total amount spent on health care in patients with certain disease states. Even though the biologic response modifiers granulocyte colony-stimulating factor (filgrastim) and granulocyte-macrophage colony-stimulating factor (sargramostim or molgramostim) are similar in name, they are chemically and biologically different. These differences result in different clinical applications. Administered after myelosuppressive antineoplastic therapy, filgrastim decreases the risk of infection. The growth factors may also be useful in patients undergoing bone marrow transplantation, in nonneutropenic patients with bacterial infections, and in patients with other disease states. Although the myeloid growth factors are somewhat expensive in terms of acquisition cost, their use is usually associated with a decrease in the risk of medical complications requiring health care expenditures, often for hospitalizations or antimicrobials. The precise cost of acquiring and administering myeloid growth factors depends on three interdependent variables: the factor used, the dosage of the drug, and the duration of therapy. Cost offsets may be more difficult to define, but they would include direct cost offsets, such as reduced episodes of febrile neutropenia and fewer, less-intense days of hospitalization or treatment. Sargramostim and molgramostim have demonstrated efficacy when given after bone marrow transplantation; filgrastim has been shown to lower infection rates by at least 50% after myelosuppressive antineoplastic therapy and in patients with severe chronic neutropenia.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗