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Biomedical subjects

K Folkers

Publications and source records attributed to K Folkers.

At least 127 records · Page 7Linked to original sources
PubMed1983

Inhibition of antidromically induced stimulation of gastric motility by substance P receptor blockade.

Electrical stimulation of the feline vagal or splanchnic nerves after hexamethonium blockade of nicotinic ganglionic transmission produces gastric contractions, suggesting antidromic activation of thin afferents. The present experiments were performed to examine whether substance P is involved as a transmitter in such gastric responses. Cats were anesthetized with chloralose, laparotomized and the adrenals were ligated. The left greater splanchnic nerve, proximal to the celiac ganglion, and the left or right cervical vagal nerve were dissected, cut and placed on electrodes for peripheral stimulation. Gastric motility was monitored with a balloon. Hexamethonium was administered i.v. as well as i.a. to the stomach. Nerve stimulations produced powerful gastric contractions, which were antagonized by large doses (approximately 0.8 mumol) of substance P administered i.a. to the stomach. Similarly, the gastric contractions elicited by vagal or splanchnic nerve stimulations were reduced to at least 60% of control by the specific substance P antagonist (D-Pro2, D-Trp7,9)-SP administered i.a. (0.4-1.3 mumol). The present results support the concept that substance P is associated with gastric excitatory motor responses, possibly elicited by antidromic activation of thin afferent nerve fibres.

Animals↗
PubMed1983

Antagonists of substance P from emphasis on position 11.

Ten analogs of substance P (SP) were designed and synthesized. The agonist and antagonist activities against SP were assayed on the isolated guinea pig ileum. The prime designs were changes of the important Met11 to include Leu11, Thr11, D-Leu11 and D-Ala11. Step-wise designs of changing D-Arg1 and D-Pro2 to the corresponding L-configurations resulted in decreasing antagonist activity. Changing Leu11 to D-Leu11 and D-Ala11 reduced antagonist activity. [D-Arg1,D-Pro2,D-Trp7,D-Trp9,Leu11]-SP is the most potent antagonist of this group of analogs, and required a 100-fold increase in the concentration of SP to give 50% of the maximal response caused by SP.

Amino Acid Sequence↗
PubMed1983

Substance P: structural requirements for the activation of brain catecholamine synthesis and locomotor activity in rats.

Intracerebroventricularly administered Arg-Pro-Lys-Pro-Gln-Gln-Phe-Gly-Leu-Met-NH2 (substance P, SP) enhanced the accumulation of DOPA after inhibition of the aromatic L-amino acid decarboxylase in the rat brain. SP also stimulated locomotor activity in a dose-dependent manner. A total of 31 structural analogues of SP were evaluated with respect to the action on brain monoamine synthesis as well as on locomotor activity. Catecholamine synthesis: SP1-10 was inactive which indicated that the [Met11]-NH2 terminal is essential for biological activity; [Leu10], [Phe7] and [Gln6] were also essential for activity; the minimum length requirement for activity was a hexapeptide amide structure. D-Amino acids in positions 8 or 9 increased activity. [D-Pro2]p-SP and [pGlu5, Gly7]-SP5-11 were active in the dopamine-rich areas, but inactive in the noradrenaline (norepinephrine)-predominant parts of the brain. The inactive [Ile7]-SP potentiated the effect of SP. Neither SP nor its analogues, with the exception of [Lys5,D-Leu8,D-Phe9]-SP5-11, increased the synthesis of 5-hydroxytryptophan (5-HTP). Locomotor activity: SP1-10 and [D-Phe9]-SP were as active as SP; [Ile7]-SP and [Ile7, Ile8]-SP were inactive and they did not antagonize the effect of SP. The results indicate that after chemical manipulation of the SP molecule it is possible to obtain great variation in activity and to dissociate to some extent the behavioural effects from those on brain catecholamine synthesis.

Animals↗
PubMed1983

Structurally restricted conjugates of the beta-subunit of the human chorionic gonadotropin to produce antisera.

Structurally restricted conjugates, beta-hCG(-NH2)4(-NHC-NH-NH2)11(-C-O-TT)1-11, were synthesized by protecting the amino and guanidino functional groups of the beta-subunit of the human chorionic gonadotropin (beta-hCG) with t-Boc groups; then, the carboxyl groups of the protected intermediate were coupled by carbodiimide reagents with basic groups of tetanus toxoid (TT). After removal of the t-Boc groups, the immunogen has a total of fifteen amino and guanidino functional groups, which may be superior to carboxyl groups, for immunologic recognition. Conjugates, prepared in non-polar and aqueous systems, had ratios of beta-hCG to TT of 13:1 and 7:1, respectively. Immunization of rabbits yielded antisera which showed an inhibition of 50% for 41-62 ng/ml, beta-hCG, at final dilution ratios of up to 1:80,000.

Animals↗
PubMed1983

Electromyographic data differentiate patients with the carpal tunnel syndrome when double blindly treated with pyridoxine and placebo.

Six typical patients with the carpal tunnel syndrome in a neurological practice were double blindly treated with pyridoxine and placebo to determine whether electromyographic data alone could identify without mistake those patients receiving pyridoxine or placebo. All six patients had a significant deficiency of vitamin B6 by the data on the erythrocyte glutamic oxaloacetic transaminase. Multiple measurements for statistical significance of EMG functions were made on temperature-controlled hands over periods of 15 to 27 days for control and final evaluation. There were significant changes in criteria of amplitude on placebo which ruled out these criteria for a double blind trial. There was no statistically significant change in any criterion of latency and conduction velocity for patients on placebo, indicating these criteria could serve for differentiation. Criteria of latency and conduction velocity showed significant changes for three patients on pyridoxine, and the extent of changes indicated a relationship to compliance. By data on latency and conduction velocity, no mistake was made in blindly identifying patients receiving pyridoxine or placebo; p less than 0.0156.

Adult↗
PubMed1983

Study of tetrahydrobiopterin and 6-methyltetrahydropterin on alcohol dependence in mice.

The literature establishes a potential link between the function of tetrahydroisoquinolines in the biological actions of alcohol and the reduced pterin cofactor needed for synthesis of certain neurotransmitters. The effect of the administration of 6-methyltetrahydropterin and tetrahydrobiopterin upon alcohol withdrawal in mice was tested. Dependence was produced by ip administration of alcohol, supplemented by alcohol delivered by a subcutaneously implanted silastic tube. Administration of the reduced pterins at relatively high doses did not reduce the magnitude of the alcohol withdrawal syndrome.

Alcoholism↗
PubMed1982

Identification of two different Q-binding sites in QH2-cytochrome c oxidoreductase, using the Q analogue n-heptadecylmercapto-6-hydroxy-5,8-quinolinequinone.

The pK and mid-point redox potential of the Q-analogue 7-(n-heptadecyl)mercapto-6-hydroxy-5,8-quinolinequinone (HMHQQ) in aqueous medium are so low that under the experimental conditions used for studying the inhibition of electron transfer in submitochondrial particles only the oxidized, anionic form is present. The KD of the analogue, determined by comparing its inhibitory effect with that of n-heptyl-4-hydroxyquinoline N-oxide, is (0.003 + 0.24 x mg protein/ml) microM. The inhibition of succinate oxidation is pH dependent, due to a pH-dependent change in the overcapacity of the QH2-oxidizing system above the Q-reducing system. If the terminal part of the respiratory chain is reduced with ascorbate, the analogue inhibits the reduction of cytochrome b by substrate in the presence of antimycin with a similar KD value. In the absence of ascorbate the KD value is 100-times higher. The reduction of cytochrome b by substrate in particles treated with 2,3-dimercaptopropanol (BAL) + O2 is also sensitive to HMHQQ, with a KD value in between the two values given above. It is concluded that the QH2 oxidase system contains two different sites for interaction with ubiquinone. The site responsible for the inhibition of steady-state electron transfer is near the Fe-S cluster, as is shown by the sensitivity to the redox state of this cluster and by the effect of HMHQQ on the EPR signal of the reduced cluster. The second site, which is similar to the antimycin-binding site, is occupied only at higher concentrations of inhibitor. The affinity of HMHQQ for this site is not affected by the redox state of the Fe-S cluster.

Animals↗
PubMed1982

Vasopressor effects of substance P and C-terminal sequences after intracisternal injection to alpha-chloralose-anaesthetized rats: blockade by a substance P antagonist.

Substance P (SP) and the C-terminal sequences octa- and penta-SP produced dose-dependent vasopressor responses, and the action was associated with mild tachycardia. The vasopressor effect of SP was counteracted by the SP antagonist [D-Pro2,D-Phe7,D-Trp9]SP given intracisternally, suggesting that central SP receptors were involved. Experiments with different sodium contents in the vehicle and with naloxone pretreatment indicate that central naloxone-sensitive opiate receptors may exist, capable of modulating the effects of SP receptor activation.

Amino Acid Sequence↗
PubMed1982

Substance P enhances cation permeability of neuronal cell lines.

Substance P stimulated the uptake of guanidinium in neuroblastoma X glioma hybrid cells and neuroblastoma cells but not in polyploid glioma cells. Guanidinium has previously been shown to pass the action potential Na+ channel in the two neuronal cell lines. Half-maximal stimulation was reached at 3 microM substance P and, with the hybrid cells, a saturation was seen above 10 microM. The analogue (D-Pro2,D-Trp7,9)-substance P, recently described as a substance P antagonist, caused a stimulation of guanidinium uptake comparable to that seen in the presence of substance P and did not inhibit the stimulation exerted by substance P. The pharmacological properties of the substance P-activated ion channel were investigated. Tubocurarine, phentolamine and propranolol blocked the substance P-stimulated guanidinium uptake with half-maximal inhibitory concentrations of 0.5, 5 and 50 microM. A similar characteristics has been found previously with the veratridine-activated Na+ channel in the cell lines investigated here. Peptides structurally related to substance P such as physalaemin and eledoisin, or others such as neurotensin, bradykinin, D-Ala2, Met5-enkephalinamide and ACTH(1-24) did not affect guanidinium uptake. In view of the high concentrations of substance P required for eliciting an effect in the cell lines, the involvement of specific receptors is questioned. A direct interaction of the peptide with the action potential Na+ channel is discussed.

Animals↗
PubMed1982

Response of vitamin B-6 deficiency and the carpal tunnel syndrome to pyridoxine.

The specific activities and percentage deficiencies of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) were determined for patients with carpal tunnel syndrome (CTS) diagnosed by clinical examination and electrical conduction data; the EGOT data revealed a severe deficiency of vitamin B-6. After double-blind treatment with pyridoxine and placebo, two physicians identified those receiving pyridoxine (clinically improved) and those receiving placebo (did not improve) without error, P less than 0.0078. Correcting a deficiency of the coenzyme at receptors of existing molecules of the apoenzyme appears to take place within days; correction of the deficiency in the number of molecules of the transaminase takes place over 10-12 weeks. The clinical response, appraised by the diminution of the symptoms of CTS, was correlated only with the restored levels of the transaminase which presumably results from a translational long-term increase in the number of molecules of EGOT by a mechanism activated by correcting a deficiency of pyridoxal 5'-phosphate. Apparent Km values of EGOT were identical for groups of patients with CTS and others without CTS but with identical specific activities, indicating that CTS is a primary deficiency of vitamin B-6 rather than one of a dependency state. Clinical improvement of the syndrome with pyridoxine therapy may frequently obviate hand surgery.

Adult↗
PubMed1982

Characterization of two substance P antisera.

The cross reactivity of two currently used substance P (SP) antisera (K 16 and K 25) with various analogues of SP, partial sequences of SP and other naturally occurring peptides were tested in a radioimmunoassay system. Both antisera were found to be C-terminal directed, this tendency being most pronounced for antiserum K 16. The capacity of antiserum K 25 to bind various SP-related peptides correlated to the previously described biological activity of these peptides on the isolated guinea pig ileum. The results thus indicate that this antiserum binds to a biologically active part of the SP-molecule.

Amino Acid Sequence↗
PubMed1982

Luteinizing hormone-releasing hormone involvement in the reproductive behavior of a male amphibian.

The present study demonstrates that an intracerebroventricular injection of luteinizing hormone-releasing hormone (LHRH) activates sexual behaviors and elevates the plasma androgen concentrations in rough-skinned newts (Taricha granulosa). The stimulatory effect of LHRH on male behavior may be a seasonal phenomenon, because LHRH stimulation of sexual behavior was only observed during the early part of the breeding season (November and December). When an active LHRH antagonist was injected into male newts, sexual behavior was suppressed. These studies indicate that endogenous LHRH is involved in regulating sexual behavior in this amphibian.

Animals↗