RESUMO
It has been found that the pharmacologically active, low molecular products obtained by digestion of telopeptides-deprived type I collagen with bacterial collagenase is a heterogenous mixture of at least 21 peptides of different molecular weight. They contain 3 to 15 amino acid residues. About 80% of them are tripeptides of the sequence Gly-Pro-X. The most abundant are two peptides: Gly-Pro-Hyp and Gly-Pro-Ala. The peptides injected into the lateral cerebral ventricle of the rat evoked some behavioral effects. They decreased the psychomotoric activity (evaluated with Lat's test) and increased the cataleptic action of haloperidol. On the other hand, they did not exert any effect on amphetamine-induced stereotypy and did not counteract the apomorphine-induced stereotypy.
Assuntos
Comportamento Animal/efeitos dos fármacos , Colágeno/farmacologia , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Fenômenos Químicos , Físico-Química , Colágeno/química , Colagenases , Hidrólise , Masculino , Dados de Sequência Molecular , Peptídeos/química , Ratos , Ratos WistarRESUMO
Rat collagen type I was digested with bacterial collagenase. The peptides obtained were submitted to gel filtration on Sephadex G-25. Two fractions differing in molecular weight (CDP I-3000 D and CDP II-1200 D) were obtained. These fractions administered to rats were found to have an inhibiting effect on the central nervous system (CNS) in Lat's test and the mobility of the animals recorded on a motimeter was found to be reduced. This effect was dependent on the peptide dose and occurred after intravenous (iv) as well as intraventricular (icv) injection.
Assuntos
Comportamento Animal/efeitos dos fármacos , Colágeno/farmacologia , Colagenase Microbiana/metabolismo , Modelos Neurológicos , Atividade Motora/efeitos dos fármacos , Pele/química , Animais , Comportamento Animal/fisiologia , Colágeno/administração & dosagem , Colágeno/metabolismo , Relação Dose-Resposta a Droga , Injeções Intravenosas , Injeções Intraventriculares , Masculino , Atividade Motora/fisiologia , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Ratos , Ratos Wistar , Estimulação QuímicaRESUMO
The effect of collagen degradation products (CDP I--molecular weight circa 3000 D and CDP II--molecular weight circa 1200 D) on the central dopaminergic system was studied. Differences in the action of both these fractions in the apomorphine stereotypy test were noted; CDP I administered to rats in a dose of 5 micrograms just before application of the drug inducing the stereotypy enhanced the stereotypic behaviour of the animals whereas a dose of 40 micrograms significantly inhibited such behaviour. CDP II, on the other hand, had no effect on this type of stereotypy. Both fractions given in doses of 15 and 40 micrograms enhanced the stereotypy induced by amphetamine. CDP I and CDP II (15 and 40 micrograms) administered 30 min before observation of the animals intensified the cataleptic action of haloperidol, whereas both fractions (CDP I and CDP II) when administered 45 min before observation reduced the catalepsy.
Assuntos
Colágeno/metabolismo , Colágeno/farmacologia , Receptores Dopaminérgicos/fisiologia , Anfetamina/farmacologia , Animais , Catalepsia , Colágeno/análise , Relação Dose-Resposta a Droga , Masculino , Peso Molecular , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/efeitos dos fármacos , Fatores de TempoRESUMO
The pharmacological activity of glycine (Gly), proline (Pro) and hydroxyproline (Hyp)--the main amino acids in collagen degradation products--was studied in comparison to the activity of all mixture of DPTC (degradation products of trihelical collagen). The investigated amino acids decreased psychomotor activity of rats, enhanced apomorphine- and amphetamine-induced stereotypy. Pro and Hyp enhanced also catalepsy, but Gly decreased the haloperidol action. Each amino acid was given adequately to its contents in DPTC. Our results indicated that hydroxyproline revealed the action on the central nervous system (CNS) in each aspect most similar to the action of DPTC mixture.