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Biomedical subjects

G Zetler

Publications and source records attributed to G Zetler.

At least 55 records · Page 3Linked to original sources

Substance P, bethanechol, 4-aminopyridine, and potassium antagonize the depressing effects of low-frequency stimulation, tetrodotoxin, procaine, and of magnesium on the field-stimulated guinea-pig vas deferens.

The twitch-response enhancing potencies of (the agonists) substance P, bethanechol, 4-aminopyridine and of potassium chloride were compared in the field-stimulated guinea-pig vas deferens. The agonists were tested after the twitching activity of the isolated organ had been reduced to an equal extent by (the antagonists) tetrodotoxin, procaine, magnesium chloride, and by decreased stimulation frequency. Further experiments were performed in the functionally denervated organ. The potencies differed with the type of antagonism of the twitch-response. This pointed at different modes of action and/or sites of mechanism of the response-enhancing compounds. The pharmacological nature of agonists and antagonists as well as the results in the denervated organ indirectly suggested a predominantly neuronal point of mechanism of the agonists. This was most obvious for substance P.

4-Aminopyridine↗

Antifibrillatory, cardiovascular and toxic effects of sparteine, butylsparteine and pentylsparteine.

The negative bathmo- ino and chronotropic effects of sparteine, butylsparteine and pentylsparteine were quantitatively determined in isolated rat atria. The antifibrillatory potency was studied in rats (aconitine arrhythmia), guinea pigs (digoxin arrhythmia) and in cats (spontaneous arrhythmia). In order to appraise the cardiovascular compatibility of these drugs, additional circulatory effects were studied in rats and cats. Acute toxicity following intravenous, intraperitoneal and oral administration was assessed in male and female mice. Pentylsparteine was more potent than sparteine and had a better therapeutic index.

Animals↗

Antagonism of cholecystokinin-like peptides by opioid peptides, morphine or tetrodotoxin.

Morphine, beta-endorphin, Met-enkephalin, and Leu-enkephalin antagonized intestinal actions of cholecystokinin octapeptide (CCK-8), caerulein, and pentagastrin in a manner partly suggesting physiologically competitive antagonism. Further, these acidic peptides (CCK-8, caerulein, pentagastrin) were much more sensitive to the actions of opioids than was angiotensin. Tetrodotoxin also caused changes in the concentration-effect curves, but these were different from the shifts due to the opioids and differentiated between CCK-8, caerulein, and pentagastrin. Naloxone did not modify the response to CCK-8 and caerulein, but completely abolished the antagonistic influence of the opioids. The potencies of morphine and the opioid peptides as antagonists of CCK-8, were of nearly the same order of magnitude. This and the presence in gut and brain of both CCK-like and opioid peptides suggests the hypothesis that these two groups of peptides interact on both myenteric and central nervous system receptors, and thus are directly involved in the regulation of both intestinal motility and satiety.

Animals↗

An attempt to differentiate the effects of angiotensin II, substance P and bradykinin on the field-stimulated guinea-pig vas deferens.

The ability of the angiotensin antagonists 1-Sar,8-Ala-angiotensin II (saralasin) and 1-Sar,8-Leu-angiotensin II (sarleusin) and the bradykinin-potentiating peptide B (BPP) to modify the twitch-enhancing effect of angiotensin II, bradykinin, and substance P, was studied in the isolated field-stimulated guinea-pig vas deferens. The twitch-enhancing effect of angiotensin, bradykinin and substance P underwent tachyphylaxis which was strongest after angiotensin. Saralasin and sarleusin were without influence on the twitch response and antagonized the effect of angiotensin, but not that of bradykinin or substance P, respectively. The features of the antagonism to angiotensin were compatible with the notion that saralasin is a competitive and sarleusin a dual antagonist. BPP did modify either the twitch response or the effects of angiotensin, bradykinin, and substance P. In the non-stimulate vas, the contracting effect of noradrenaline did not undergo tachyphylaxis and was not mofified by angiotensin, bradykinin, or substance P. It is concluded that there exist in the guinea-pig vas specific peptide receptors, one of them having the properties of a "typical" angiotensin receptor.

Angiotensin II↗

A cholecystokinin-like peptide in crude substance P from human and bovine brain.

The subfractions of crude substance P (SP), Fa, Fb, and Fc, were assayed for SP-like activity (SP-LA) and cholecystokinin octapeptide-like activity (CCK-8-LA) using radioimmunoassays (RIAs) and bioassays. Crude SP preparations from total human and bovine brains, cortex, and subcortex (amygdala, substantia nigra) contain CCK-8-LA as well as SP-LA. Most of SP-LA was contained in Fb, whereas most of CCK-8-LA was in Fc. Fa gave ambiguous results. Pharmacological results previously obtained with Fc may reflect the activity of CCK-like peptide(s).

Animals↗

Crude substance P from brain contains a cholecystokinin-like peptide.

The subfractions Fa, Fb, and Fc of crude substance P (SP) preparations made from human and bovine brains were analysed for SP and the COOH-terminal octapeptide of cholecystokinin (CCK-8). The methods were specific radioimmunoassays (RIAs) for SP and CCK-8, and bioassays on isolated organs of the guinea pig: the ileum, the gallbladder and the field-stimulated vas deferens. 1. In bioassays of synthetic peptides the vas deferens reacted specifically to SP and the gallbladder to CCK-8. 2. RIAs and bioassays revealed unequivocally that most of SP-like activity was present in Fb, while Fc contained mainly CCK-8-like activity. Varying results were obtained with Fa. 3. The pharmacologically active principle of Fc is CCK-8 or a closely related peptide. Earlier results concerning the pharmacological and neurochemical properties of Fc must be ascribed to this peptide.

Animals↗

Effects of simple indoles, noradrenaline, nicotine, and tyramine on action potential and contractility of the isolated guinea-pig papillary muscle.

1. Simultaneous recordings of both the transmembrane action potential and the contractions were made in isolated electrically driven papillary muscles of the guinea pig in order to compare the effects of 6-methoxyindole (6-MOI), 3-methylindole (3-MI) and 5-methylindole (5-MI) with those of noradrenaline (1.2 - 10(-6) M), nicotine (2 - 10(-5) M), and tyramine (5.8 - 10(-6) M). 2. Noradrenaline, nicotine, tyramine and 6-MOI (5.4 - 10(-4) M) enhanced the contractility whilst 3-MI (3.8 and 7.8 - 10(-4) M) and 5-MI (1.9 and 3.8 - 10(-4) M) had only irregular effects. The active compounds shortened and time-to-peak tension and increased the rate of relaxation. 3. The duration of the action potential was prolonged by noradrenaline, nicotine, and tyramine, but shortened by 3-MI, 5-MI, and 6-MOI. 4. The results showed that the effect of drugs on the action potential are not necessarily linked to those on contractility.

Action Potentials↗

Haloperidol catalepsy in grouped and isolated mice.

A method was worked out to assess in a quantitative and dose-dependent way the development of catalepsy of mice after low doses of haloperidol. This method was also capable of detecting the anticataleptic effect of phenytoin and the catalepsy-enhancing effect of nikethamide. After 4 weeks' isolation, the mice became aggressive and revealed increased susceptibility to the cataleptic effect of haloperidol. The analysis of the data indicates that in these experiments altered central mechanisms were more important than changes of the peripheral pharmacokinetics of haloperidol.

Animals↗