Gene/Protein Disease Symptom Drug Enzyme Compound
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 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dose-effect relationships of intraventricularly injected bradykinin, Gly-Arg-Met-Lys-bradykinin (GAML-bradykinin), synthetic substance P and angiotensin II on lever-lifting behavior of rabbits in a variable-interval (VI) 72-second schedule of sweetened water presentation were determined. All peptides used caused dose-dependent decreases in overall rates of VI responding during the experimental session in the following order of potency: angiotensin II greater than bradykinin = substance P greater than GAML-bradykinin. The angiotensin II dose-effect curve was less steep than those of the other peptides. The administration of nearly equimolar doses of the bradykinin potentiating peptides, BPP5a and BPP9a, slightly decreased overall VI response rates and caused a 10- to 20-fold potentiation of the rate-decreasing effect of bradykinin on VI responding. Both angiotensin II and bradykinin caused pauses in responding of dose-dependent duration at the beginning of the experimental session that were followed by normal VI responding. The effect of GAML-bradykinin on VI performance was similar to that of bradykinin and angiotensin II but had a delay of onset of 3 to 6 minutes. In contrast, substance P caused actual decreases in response output and pauses of variable duration interspersed between periods of regular VI responding. At the doses used, both bradykinin-potentiating peptides caused uniform decreases in VI responding throughout the experimental session. Gross behavioral changes caused by the peptides were also observed. After the intraventricular injection of bradykinin or GAML-bradykinin, rabbits showed decreased motility, ptosis, miosis and lowered ears; after angiotensin II, animals remained motionless but with wide open eyes, fully raised ears and no miosis. In turn, substance P caused restlessness and increased locomotion. These results together with reported evidence on other powerful central actions of bradykinin, angiotensin and substance P and on the existence of components of their releasing and destroying enzymatic systems in the brain suggest that linear peptides may play a role in the functioning of the central nervous system.
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PMID:Effect of intracerebroventricular bradykinin and related peptides on rabbit operant behavior. 109 6

Effects of dl-1-(4-amino-3-chloro-5-trifluoromethyl-phenyl)-2-tert.-butylamino-etha nol hydrochloride (mabuterol) on the central nervous system, the striated muscle and the carbohydrate and lipid metabolism were investigated in comparison with those of isoprenaline and salbutamol. Mabuterol caused the following changes in behavior: increased touch response (10 mg/kg p.o.), decreased spontaneous movement and ptosis (30 and 100 mg/kg p.o., resp.), observed for 240-300 min. Mabuterol (5 mg/kg p.o. and 2.5 mg/kg s.c.) prolonged the sleeping time induced by hexobarbital Na, but not dose-dependently. Mabuterol depressed reactive movement at 80 mg/kg p.o. and 40 mg/kg s.c. in the rotarod test, at 160 mg/kg p.o. and 40 mg/kg s.c. in the traction test and at 200 mg/kg p.o. and 160 mg/kg s.c. in the inclined plane test in mice, whereas isoprenaline and salbutamol were almost ineffective. Analgesic activity of mabuterol was found in the acetic acid writhing test but not in the bradykinin-induced nociception test. An anticonvulsive effect was not observed. Mabuterol (10 mg/kg i.v.) produced a change in the spontaneous EEG of one of three rabbits, showing synchronization of cortical activity with sedation. Equipotent dose (i.v.) ratios of mabuterol to isoprenaline were 10.2, 30 and 133 in the depression of incomplete tetanic contraction of cat soleus muscle, hypotensive effect and tachycardia respectively, whereas neither indirect nor direct electrical stimulation induced contraction of diaphragm and gastrocnemius muscle was affected. Equipotent dose (s.c.) ratios of mabuterol to isoprenaline were 2.07, 4.64 and 3.21 in increasing plasma levels of glucose, lactic acid and free fatty acids respectively. Mabuterol caused no remarkable change in myocardial glycogen content.
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PMID:Pharmacological studies of mabuterol, a new selective beta 2-stimulant. III: Effects on the central nervous system, striated muscle and carbohydrate and lipid metabolism. 615 58