Iridium assisted S-H and C-H activation of benzaldehyde thiosemicarbazones. Synthesis, structure and electrochemical properties of the resulting complexes

Reaction of five 4-R-benzaldehyde thiosemicarbazones (R = OCH₃, CH₃, H, Cl and NO₂) with [Ir(PPh₃)₃Cl] in refluxing ethanol in the presence of a base (NEt₃) affords complexes of three different types, viz. 1-R, 2-R and 3-R. In the 1-R complexes the thiosemicarbazone is coordinated to iridium as a monoanionic bidentate N,S-donor forming a four-membered chelate ring. Two triphenylphosphines, a hydride and a chloride are also coordinated to the metal center. The 2-R complexes are very similar in composition and stereochemistry to the corresponding 1-R complexes, except that a second hydride is bound to iridium instead of the chloride. In the 3-R complexes, the thiosemicarbazones are coordinated to iridium as dianionic tridentate C,N,S-donors forming two adjacent five-membered chelate rings. Two triphenylphosphines and a hydride are also coordinated to the metal center. Structures of the 1-NO₂, 2-NO₂ and 3-NO₂ complexes have been determined by X-ray crystallography. Reaction of the same 4-R-benzaldehyde thiosemicarbazones with [Ir(PPh₃)₃Cl] in refluxing toluene in the presence of NEt₃ affords complexes of two types, viz. 3-R and 4-R. The 4-R complexes are very similar in composition and stereochemistry to the corresponding 3-R complexes, except that a chloride is bound to iridium instead of the hydride. Structure of the 4-CH₃ complex has been determined by X-ray crystallography. In all the complexes the two PPh₃ ligands are trans. All the complexes show intense MLCT transitions in the visible region. Cyclic voltammetry on the complexes shows an Ir(III)-Ir(IV) oxidation on the positive side of SCE followed by an oxidation of the coordinated thiosemicarbazone. A reduction of the coordinated thiosemicarbazone is also observed on the negative side of SCE.     

Ruthenium mediated C-H activation of benzaldehyde thiosemicarbazones: Synthesis, structure and, spectral and electrochemical properties of the resulting complexes

Reaction of five 4R-benzaldehyde thiosemicarbazones (R = OCH₃, CH₃, H, Cl and NO₂) with [Ru(PPh₃)₃(CO)(H)Cl] in refluxing methanol in the presence of a base (NEt₃) affords complexes of two different types, viz. 1-R and 2-R. In the 1-R complexes the thiosemicarbazone is coordinated to ruthenium as a dianionic tridentate C,N,S-donor via C-H bond activation. Two triphenylphosphines and a carbonyl are also coordinated to ruthenium. The tricoordinated thiosemicarbazone ligand is sharing the same equatorial plane with ruthenium and the carbonyl, and the PPh₃ ligands are mutually trans. In the 2-R complexes the thiosemicarbazone ligand is coordinated to ruthenium as a monoanionic bidentate N,S-donor forming a four-membered chelate ring with a bite angle of 63.91(11)°. Two triphenylphosphines, a carbonyl and a hydride are also coordinated to ruthenium. The coordinated thiosemicarbazone ligand, carbonyl and hydride constitute one equatorial plane with the metal at the center, where the carbonyl is trans to the coordinated nitrogen of the thiosemicarbazone and the hydride is trans to the sulfur. The two triphenylphosphines are trans. Structures of the 1-CH₃ and 2-CH₃ complexes have been determined by X-ray crystallography. All the complexes show intense transitions in the visible region, which are assigned, based on DFT calculations, to transitions within orbitals of the thiosemicarbazone ligand. Cyclic voltammetry on the complexes shows two oxidations of the coordinated thiosemicarbazone on the positive side of SCE and a reduction of the same ligand on the negative side.     

Quaternary structure predictions and estimation of mutational effects on the free energy of dimerization of the OMPLA protein

This study represents an extension to the outer membrane phospholipase A protein (OMPLA) of the docking-based protocols previously developed for quaternary structure predictions of transmembrane oligomeric proteins and for estimating mutational effects on the thermodynamics of protein–protein and protein–DNA association.Predictions of the likely architecture of OMPLA homo-dimers were carried out on 31 different forms of the monomer, 30 of which were variants of the unbound state. In all the test cases but the ones characterized by combined deletions of the 98–110 and 145–153 segments (L2 and L3, respectively), native-like complexes could be predicted, independent of the bound or unbound state of the structural model, of side chain conformation and presence or absence of amino acid deletions at the putative inter-monomer interface.The protocol for estimating mutational effects on the thermodynamics of protein–protein association proved effective as well. In fact, it was possible to estimate correctly the effects of five mutants on the free energy of dimerization of the sulfonylated form of OMPLA.The integrity of L2 and either one of the L1, L3 and L4 loops turned out to be more important than sulfonylation for the achievement of the native dimeric architecture. On the other hand, sulfonylation seems to be essential for a favorable dimerization energetics.     

Structural effects on electrochemical properties of the carboxamide complexes [Ni(Mebpb)] and [Ni(Mebqb)]

Two Ni(II) complexes of the dianionic ligands, Mebpb²⁻, [H₂Mebpb = N,N′-bis(pyridine-2-carboxamido)-4-methylbenzene] and Mebqb²⁻, [H₂Mebqb = N,N′-bis(quinoline-2-carboxamido)-4-methylbenzene] have been synthesized and characterized by elemental analyses, IR, and UV-Vis spectroscopy. The crystal and molecular structures of [Ni(Mebpb)], (1), and [Ni(Mebqb)], (2), were determined by X-ray crystallography. Both complexes exhibit distorted square-planar NiN₄ coordination figures with two short and two long Ni-N bonds (Ni-N ∼1.84 and ∼1.95 Å, respectively). The electrochemical behavior of these complexes with the goal of evaluating the structural effects on the redox properties has been studied.     

Double-headed protease inhibitors from black-eyed peas. VI. Singlet-singlet energy transfer and other optical studies on the structure of trypsin and chymotrypsin complexes.

The geometry of the binary and ternary complexes of two black-eyed pea inhibitors with trypsin and chymotrypsin has been established by distance measurements using the technique of singlet-singlet energy transfer. Triangulation of measured distances in the ternary double-headed complex of the trypsin-chymotrypsin inhibitor (BEPCI) with trypsin and chymotrypsin limits the possible structural models for this complex to those in which the center to center distance between trypsin and chymotrypsin is about 64 A, the distance from the center of trypsin to the single fluorescently labeled tyrosyl residue of the BEPCI dimer is about 33 A, and the distance between the chymotrypsin center and the labeled tyrosine of the inhibitor is about 43 A. Energy transfer results for the trypsin inhibitor (BEPTI) complexes show conclusively that the weak trypsin site is structurally analogous to the strong chymotrypsin binding site of BEPCI. The weak chymotrypsin binding site of BEPTI is structurally analogous to the strong trypsin sites of BEPCI and BEPTI. Corresponding distances in binary and ternary complexes are the same, indicating that little or no structural rearrangement occurs when the ternary complexes are formed. Complex formation was shown to involve tryptophan and tryosine residues of both trypsin and chymotrypsin as judged by absorption and circular dichroism difference spectroscopy. In addition, circular dichroism difference spectra revealed some disulfide contributions.     

Steric effects on the substitution of pentaamine-chromium(III) and -rhodium(III) complexes. Anation reaction rate constants as an indicative of the dissociative shift of the mechanism on crowding the [M(RNH2)5H2O] (M = Rh, R = H, Me, Et, Pr; M = Cr, R = H, Me, Pr) complexes

The kinetics of the anation reactions of [M(RNH₂)₅H₂O]³⁺ (M = Rh, R = H, Me, Et, Pr; M = Cr, R = H, Me, Pr) with several ligands (H₃PO₄/H₂PO₄⁻, H₃PO₃/H₂PO₃⁻, CF₃COO⁻, Br⁻, Cl⁻, SCN⁻) have been studied at different temperatures and acidities at I = 1.0 M (LiClO₄. Results obtained for the anation rate constants and thermal activation parameters are compared with the previously published data for R = H, in order to establish the effects of the amine substituents in the reaction mechanism proposed for the substitution reactions of these complexes. The results obtained are interpreted on the basis of a mechanism where the bond formation process is more important in the substitution on M = Cr complexes than in that of the M = Rh complexes, as already pointed out for the published ΔΛ^≠ values for the water exchange on these systems. A simple Langford-Gray classification becomes inadequate to describe these situations where the increase of the steric demand of the amine substituents shifta the I_a-I_d classification to the I_d side, although no dramatic changes in the reaction mechanism are found. It is concluded that a More O'Ferall ‘continuous’ type of approach to the mechanism classification of the substitution reactions is much more useful in this case.     

The propensity of alkoxide and aryloxide derivatives of tungsten carbonyls to aggregate in solution. Synthesis and X-ray structures of dinuclear, trinuclear and tetranuclear complexes derived from the MeOW(CO)5 anion

The complex [Et₄N][W(CO)₅OMe] (1) has been prepared from the reaction of the photochemically generated W(CO)₅THF adduct and [Et₄N][OH] in methanol. Complex 1 was shown to undergo rapid CO dissociation in THF to quantitatively provide the dimeric dianion, [W(CO)₄OMe]₂²⁻. The resulting THF insoluble salt [Et₄N]₂[W(CO)₄OMe]₂ (2) has been structurally characterized by X-ray crystallography, with the doubly bridging methoxide ligands being in an anti configuration. Complex 2 was found to subsequently react with excess methoxide ligand in a THF slurry to afford the face-sharing octahedron complex [Et₄N]₃[W₂(CO)₆(OMe)₃] (3) which contains three doubly bridging methoxide groups. In the absence of excess methoxide ligand complex 2 cleanly yields the tetrameric complex [Et₄N]₄[W(CO)₃OMe]₄ (4) which has been structurally characterized as a cubane-like arrangement with triply bridging μ³-methoxide groups and W(CO)₃ units. Although complex 3 was not characterized in the solid state, the closely related glycolate derivative [Et₄N]₃[W₂(CO)₆(OCH₂CH₂OH)₃] (5) was synthesized and its structure determined by X-ray crystallography. The trianions of complex 5 are linked in the crystal lattice by strong intermolecular hydrogen bonds. Crystal data for 2: space group P2₁/n, a = 7.696(2), b = 22.019(4), c = 9.714(2) Å, β = 92.22(3)°, Z = 4, R = 6.43%. Crystal data for 4: space group Fddd, a = 12.433(9), b = 24.01(2), c = 39.29(3) Å, Z = 8, R = 8.13%. Crystal data for 5: space group P2₁2₁2₁, a = 11.43(2), b = 12.91(1), c = 29.85(6) Å, Z = 8, R = 8.29%. Finally, the rate of CO ligand dissociation in the closely related aryloxide derivatives [Et₄N][W(CO)₅OR] (R = C₆H₅ and 3,5-F₂C₆H₃) were measured to be 2.15 × 10⁻² and 1.31 × 10⁻³ s⁻¹, respectively, in THF solution at 5°C. Hence, the value of the rate constant of 2.15 × 10⁻² s⁻¹ establishes a lower limit for the first-order rate constant for CO loss in the W(CO)₅OMe⁻ anion, since the methoxide ligand is a better π-donating group than phenoxide.     

Influence of ligands’ peripheral substituents on the structure, magnetochemical and electrochemical behaviour of complexes containing a Cu2O2 butterfly core

New polydentate open structure ligands H₃L1 and H₃L2 were synthesized by the condensation of 2,6-diformyl-4-tert-butylphenol and corresponding N-R-o-phenylenediamines (R = Ac and R = Boc). Treating of the ligands with copper trimethylacetate leads to binuclear copper complexes with dissimilar Cu₂O₂ cores, the structures of which were solved by X-ray diffraction analysis. The electrochemical properties of both complexes were studied; the observed redox transitions were assigned to specific redox-active sites of the molecule. These assignments were confirmed by DFT calculations of the electronic structure of binuclear complexes. Both complexes exhibit antiferromagnetic behaviour, as confirmed by variable-temperature magnetic studies.     

The effects of starvation on the sodium, potassium, water and free amino acid content of parietal muscle from Agonus cataphractus.

1. The levels of the individual free amino acids, K, Na and water present in parietal muscle were measured in fish starved for periods of 3-115 days. 2. The Na and water content progressively increased relative to dry weight of tissue during the starvation period whereas an initial increase in the K content up to 67 days was followed by a decrease to near the normal fed level by 115 days. The ammonia content remained essentially stable over the same period. 3. The essential free amino acid content tended to follow the muscle sodium pattern while the non-essential amino acids and taurine gave results somewhat similar to those of potassium. 4. The net result of these changes is that the Na, K and total free amino acid concentration is maintained within fairly narrow limits relative to the tissue water content during 11-67 days of the starvation period under the experimental conditions used.     

IRBAS: An online database to collate,analyze, and synthesize data on the biodiversity and ecology of intermittent rivers worldwide

Key questions dominating contemporary ecological research and management concern interactions between biodiversity, ecosystem processes, and ecosystem services provision in the face of global change. This is particularly salient for freshwater biodiversity and in the context of river drying and flow‐regime change. Rivers that stop flowing and dry, herein intermittent rivers, are globally prevalent and dynamic ecosystems on which the body of research is expanding rapidly, consistent with the era of big data. However, the data encapsulated by this work remain largely fragmented, limiting our ability to answer the key questions beyond a case‐by‐case basis. To this end, the Intermittent River Biodiversity Analysis and Synthesis (IRBAS; http://irbas.cesab.org ) project has collated, analyzed, and synthesized data from across the world on the biodiversity and environmental characteristics of intermittent rivers. The IRBAS database integrates and provides free access to these data, contributing to the growing, and global, knowledge base on these ubiquitous and important river systems, for both theoretical and applied advancement. The IRBAS database currently houses over 2000 data samples collected from six countries across three continents, primarily describing aquatic invertebrate taxa inhabiting intermittent rivers during flowing hydrological phases. As such, there is room to expand the biogeographic and taxonomic coverage, for example, through addition of data collected during nonflowing and dry hydrological phases. We encourage contributions and provide guidance on how to contribute and access data. Ultimately, the IRBAS database serves as a portal, storage, standardization, and discovery tool, enabling collation, synthesis, and analysis of data to elucidate patterns in river biodiversity and guide management. Contribution creates high visibility for datasets, facilitating collaboration. The IRBAS database will grow in content as the study of intermittent rivers continues and data retrieval will allow for networking, meta‐analyses, and testing of generalizations across multiple systems, regions, and taxa.     

An estimation of the effects of synthetic auxin and cytokinin and the time of their application on some morphological and physiological characteristics of Medicago x varia T. Martyn

The aim of the experiment was to determine the effects of synthetic auxin and cytokinin and the time of their application on some morphological and physiological characteristics of Medicago x varia T. Martyn grown under controlled conditions. The experiment was to check whether an application of exogenous hormones during vegetative and generative stages of the plant had an effect on above-ground mass development, on nitrate reductase activity and on plastid pigments content. Experiment factor was synthetic auxin and cytokinin and the date of their application. Auxin was applied in the form of a synthetic indole-3-butyric acid, while cytokinin was sprayed as synthetic 6-benzylaminopurine. The control plants were treated with distilled water. Depending on the experimental variant, spraying was applied at the sixth true leaf stage and at the first flower bud stage. The research showed that the response of the alfalfa plants to the application of cytokinin and auxin was not uniform. It seems that the most effective was the application of a mixture of them both but only during the vegetative stage.Additionally, cytokinin caused an increase in plastid pigments content in alfalfa leaves. On the other hand, a mixture of auxin and cytokinin triggered the highest nitrate reductase activity in alfalfa roots and raised the ratio of total chlorophyll content to carotenoids. Synthetic auxin caused the decrease of the levels of most parameters compared to the control.     

Studies on the synthesis,characterisation and antimicrobial activity of new Co(II), Ni(II) and Zn(II) complexes of Schiff base derived from ninhydrin and glycine

Summary For the first time, Co(II), Ni(II) and Zn(II) complexes have been synthesized involving an intermediate Schiff base, indane-1,3-dione-2-imine-N-acetic acid the condensed product of ninhydrin and glycine. These coloured complexes were characterised by elemental analysis, molar conductivity, thermogravimetric analyses/differential thermal analysis, infrared, magnetic susceptibility, NMR and electronic spectral studies. Mechanisms for their formation have been proposed. The experimental studies reveal that the complexes possess octahedral stereochemistry whereas the Schiff base behaves as a monobasic tridentate ligand. A molecular structure for the metal complexes is also proposed. A comparative study of the antimicrobial activity of ninhydrin and the corresponding metal complexes againstEscherichia coli, Proteus mirabilis, Staphylococcus aureus andStreptococcus faecalis has been undertaken and the results are discussed.     

Cooperative effects of potassium, magnesium, and magnesium-ADP on the release of Escherichia coli dihydrofolate reductase from the chaperonin GroEL.

Previous investigation has shown that at 22 degrees C and in the presence of the chaperonin GroEL, the slowest step in the refolding of Escherichia coli dihydrofolate reductase (EcDHFR) reflects release of a late folding intermediate from the cavity of GroEL (Clark AC, Frieden C, 1997, J Mol Biol 268:512-525). In this paper, we investigate the effects of potassium, magnesium, and MgADP on the release of the EcDHFR late folding intermediate from GroEL. The data demonstrate that GroEL consists of at least two conformational states, with apparent rate constants for EcDHFR release that differ by four- to fivefold. In the absence of potassium, magnesium, and ADP, approximately 80-90% of GroEL resides in the form with the faster rate of release. Magnesium and potassium both shift the distribution of GroEL forms toward the form with the slower release rate, though cooperativity for the magnesium-induced transition is observed only in the presence of potassium. MgADP at low concentrations (0-50 microM) shifts the distribution of GroEL forms toward the form with the faster release rate, and this effect is also potassium dependent. Nearly identical results were obtained with a GroEL mutant that forms only a single ring, demonstrating that these effects occur within a single toroid of GroEL. In the presence of saturating magnesium, potassium, and MgADP, the apparent rate constant for the release of EcDHFR from wild-type GroEL at 22 degrees C reaches a limiting value of 0.014 s(-1). For the single ring mutant of GroEL, the rate of EcDHFR release under the same conditions reaches a limiting value of 0.024 s(-1), suggesting that inter-ring negative cooperativity exists for MgADP-induced substrate release. The data suggest that MgADP preferentially binds to one conformation of GroEL, that with the faster apparent rate constant for EcDHFR release, and induces a conformational change leading to more rapid release of substrate protein.     

Effects of activation of skin ion channels TRPM8, TRPV1, and TRPA1 on the immune response. Comparison with effects of cold and heat exposure

The effects of pharmacological stimulation of skin ion channels TRPA1, TRPM8, TRPV1 on the immune response are presented. These effects are compared with the effects of different types of temperature exposures - skin cooling, deep cooling, and deep heating. This analysis allows us to clear the differences in the influence on the immune response of thermosensitive ion channels localized in the skin; (2) whether the changes in the immune response under temperature exposures are due to these thermosensitive ion channels. Experiments were performed on Wistar rats. For stimulation of TRPM8 ion channel, an application to the skin of 1% menthol was used, for TRPA1 - 0.04% allylisotiocianate, and for TRPV1 - capsaicin in a concentration of 0.001.The antigen binding in the spleen was two-times stimulated by activation of the cold-sensitive ion channel TRPM8 and much weaker by activation of warm-sensitive TRPV1 (by 15%), and another cold-sensitive ion channel TRPA1 (by 40%). Only the stimulation of TRPA1 significantly (by 140%) increased antibody formation in the spleen, while TRPM8 had practically no effect on this process, and activation of TRPV1 significantly (by 60%) inhibited antibody formation. Stimulation of the TRPM8 ion channel significantly (by 60%) reduced the level of IgG in the blood, which is believed to control of infectious diseases.The obtained results show that pharmacological activation of the skin TRPA1, TRPM8, TRPV1 ion channels can differently affect the immune system. At the epicenter of changes there were the antigen binding and antibody formation in the spleen, as well as the level of IgG in the blood. Exactly stimulation of the TRPM8 ion channel determines the changes in the immune response when only the skin is cooling, while at deep body heating, the changes in the immune response are mostly determined by the activation of the skin TRPV1 ion channel.     

Delayed light studies on photosynthetic energy conversion. VII. Effect of the high energy state, coupled to 2,3,5,6-tetramethyl p-phenylenediamine-catalyzed cyclic electron flow, on millisecond emission from chloroplasts and digitonin subchloroplast particles

The effect of 2,3,5,6-tetramethyl p-phenylenediamine-catalyzed cyclic electron flow on millisecond delayed light emission from chloroplasts has been compared to the effect on subchloroplast particles. Non-cyclic electron flow of both chloroplasts and subchloroplast particles was blocked with 3-(3,4-dichlorophenyl)-1,1-dimethylurea. 2,3,5,6-tetramethyl p-phenylenediamine-catalyzed cyclic electron flow increased the millisecond delayed emission by 2–4 times in both chloroplasts and subchloroplast particles. Uncoupling conditions which collapse only the pH gradient component of the proton motive force reduced the 2,3,5,6-tetramethyl p-phenylenediamine stimulation of delayed light in chloroplasts but not in particles. The 2,3,5,6-tetramethyl p-phenylenediamine stimulation of delayed light in particles was sensitive to uncoupling conditions which are presumed to destroy the transmembrane potential. Energy transfer inhibitors were without effect on the 2,3,5,6-tetramethyl p-phenylenediamine stimulation in both chloroplasts and particles.

The 2,3,5,6-tetramethyl p-phenylenediamine stimulation of millisecond delayed emission appears to reflect the particular form of the proton motive force; in chloroplasts it seems to be correlated with the proton concentration gradient, whereas in particles it is more closely correlated with the transmembrane potential.     

Synthetic, EPR spectroscopic, magnetic and X-ray crystallographic structural studies on copper(II) complexes of the tridentate N2S donor ligand formed from 6-methyl-2-formylpyridine and S-methyldithiocarbazate (Hmpsme)

New copper(II) complexes of general empirical formula, Cu(mpsme)X · xCH₃COCH₃ (mpsme = anionic form of the 6-methyl-2-formylpyridine Schiff base of S-methyldithiocarbazate; X = Cl, N₃, NCS, NO₃; x = 0, 0.5) have been synthesized and characterized by IR, electronic, EPR and susceptibility measurements. Room temperature μ_eff values for the complexes are in the range 1.75-2.1 μ_B typical of uncoupled or weakly coupled Cu(II) centres. The EPR spectra of the [Cu(mpsme)X] (X = Cl, N₃, NO₃, NCS) complexes reveal a tetragonally distorted coordination sphere around the mononuclear Cu(II) centre. We have exploited second derivative EPR spectra in conjunction with Fourier filtering (sine bell and Hamming functions) to extract all of the nitrogen hyperfine coupling matrices. While the X-ray crystallography of [Cu(mpsme)NCS] reveals a linear polymer in which the thiocyanate anion bridges the two copper(II) ions, the EPR spectra in solution are typical of a magnetically isolated monomeric Cu(II) centres indicating dissociation of the polymeric chain in solution. The structures of the free ligand, Hmpsme and the {[Cu(mpsme)NO₃] · 0.5CH₃COCH₃}₂ and [Cu(mpsme)NCS]_n complexes have been determined by X-ray diffraction. The {[Cu(mpsme)NO₃] 0.5CH₃COCH₃}₂ complex is a centrosymmetric dimer in which each copper atom adopts a five-coordinate distorted square-pyramidal geometry with an N₂OS₂ coordination environment, the Schiff base coordinating as a uninegatively charged tridentate ligand chelating through the pyridine and azomethine nitrogen atoms and the thiolate, an oxygen atom of a unidentate nitrato ligand and a bridging sulfur atom from the second ligand completing the coordination sphere. The [Cu(mpsme)(NCS)]_n complex has a novel staircase-like one dimensional polymeric structure in which the NCS⁻ ligands bridge two adjacent copper(II) ions asymmetrically in an end-to-end fashion providing its nitrogen atom to one copper and the sulfur atom to the other.     

Differential effects of histamine, vasoactive intestinal polypeptide, prostaglandin E2 and somatostatin on cyclic AMP-dependent protein kinase activation in gastric glands isolated from the guinea pig fundus and antrum

Histamine, vasoactive intestinal polypeptide (VIP), secretin and prostaglandin E2 (PGE2) stimulate cyclic AMP-dependent protein kinase activity in gastric glands isolated from the guinea pig fundus and antrum. The effects are observed in the absence of any cyclic AMP phosphodiesterase inhibitor and maximal stimulation of the protein kinases occurs within 0.5 min of incubation at 20 degrees C. As shown by dose-response studies, VIP is equally potent in the antrum as in the fundus (identical values of the activation constant are found in both types of gland, Ka = 2.5 . 10(-9) M); a similar situation occurs for PGE2 action (but with Ka = 2.0 . 10(-8) M), whereas the potency of histamine is higher in the fundus (ka = 8.0 . 10(-6)M) than in the antrum (Ka = 5.0 . 10(-5) M). Secretin also increases the protein kinase activity ratio but with a 1000 times lower potency than VIP. In fundic glands, histamine (10(-3) M) is the activator of by far the greatest efficacy (increasing protein kinase activity at 4 times of the basal value) as compared with the effect obtained with 10(-6) M PGE2 (2.7 times) and 10(-7) M VIP (1.4 times). In contrast, VIP has greater efficacy (2.3 times) than histamine (2.1 times) in antral glands, whereas PGE2 is equally active in the two parts of the gastric mucosa. In addition, somatostatin (10(-6) M) inhibits partially (30%) and specifically the protein kinase activation stimulated by histamine, whereas it has no effect on VIP- and PGE2-induced activation. The results are consistent with increased cyclic AMP levels in response to these effectors in this system. A physiological role of histamine on acid-secreting parietal cells, of VIP on nonparietal cells and of PGE2 on both cell types, mediated by the cyclic AMP/protein kinase system is proposed.