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Biomedical subjects

P Hamosh

Publications and source records attributed to P Hamosh.

At least 37 records · Page 2Linked to original sources
PubMed1991

Cocaine acts in the central nervous system to inhibit sympathetic neural activity.

Cocaine was administered i.v. to decerebrate cats while monitoring cardiac preganglionic sympathetic nerve activity (SNA), arterial blood pressure (BP) and heart rate (HR). Cocaine, 4 mg/kg i.v., reduced SNA by 55 +/- 6%, but did not significantly affect BP or HR. Cocaine, in doses that were ineffective by the i.v. route, was administered into the vertebral artery and produced decreases in SNA, BP and HR in anesthetized cats. Administration of cocaine into the carotid artery was without effect. Topical administration of cocaine to the intermediate area of the ventrolateral medullary surface (25 micrograms/side) evoked hypotension and bradycardia. Nisoxetine, an inhibitor of norepinephrine uptake, applied bilaterally to the intermediate area (30 micrograms/side) exerted a similar hypotensive effect. Lidocaine administered in doses equivalent to those of cocaine had no significant effect on SNA when given i.v. or on BP when given into the vertebral artery. These results indicate that cocaine inhibits central sympathetic outflow and that the site of action appears to be in the hindbrain at a site that is reached by placement of the drug at the intermediate area of the ventrolateral medulla. The data also indicate that the mechanism of action of cocaine to inhibit sympathetic outflow may be unrelated to its local anesthetic action and may involve inhibition of catecholamine uptake in the ventrolateral medulla.

Animals↗
PubMed1990

Factors determining whether cocaine will potentiate the cardiac effects of neurally released norepinephrine.

The purpose of the present study was to re-evaluate the effects of cocaine on cardiac responses elicited by sympathetic nerve stimulation. Cats anesthetized with pentobarbital and subjected to spinal cord transection were used. Control heart rate increases were obtained to submaximal stimulation of postganglionic accelerator nerves, before and after i.v. bolus doses of cocaine ranging from 0.0625 to 2.0 mg/kg. Maximal potentiation of heart rate increases elicited by nerve stimulation were observed with 0.25 mg/kg. In precocaine controls, stimulation increased sinus rate by 31 +/- beats/min; 30 sec to 1 min after cocaine (0.25 mg/kg), stimulation increased sinus rate by 55 +/- beats/min. Maximal potentiation (80 +/- 10%) was observed at 30 sec to 1 min after cocaine administration, and was usually over by 45 to 60 min later. Cocaine was repeated twice (0.25 mg/kg i.v.) at hourly intervals and the magnitude of potentiation was only 19 +/- 6 and 24 +/- 4%, respectively, indicating that tachyphylaxis had developed toward cocaine's potentiating effect. Dose-response studies indicated that as little as 0.0625 mg/kg of cocaine can potentiate heart rate increases elicited by sympathetic nerve stimulation. Doubling the dose to 0.125 mg/kg, and again to 0.25 mg/kg, resulted in a linear dose-related increase in the magnitude of potentiation. However, doubling the dose again to 0.5 mg/kg and increasing this dose by 4-fold to 2 mg/kg did not result in additional potentiation. Indeed, there was a significant drop-off in the magnitude of potentiation to nerve stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effect of intralipid infusion on lecithin:cholesterol acyltransferase and lipoprotein lipase in young rats.

We compared the effects of Intralipid and dextrose infusion on plasma lecithin:cholesterol acyltransferase (LCAT), plasma lipid profiles and lipolytic activity. We used 5-week-old male Sprague-Dawley rats which were given total parenteral nutrition (TPN) with either Intralipid (3 g/kg body weight) or an equicaloric amount of 25% dextrose in the presence or absence of heparin (1 or 10 IU/ml of TPN). 40 min after the end of 4 h of infusion, plasma LCAT activity was significantly decreased (P less than 0.001), while total cholesterol and free fatty acid levels were significantly (P less than 0.05) increased in rats given Intralipid as compared to those given dextrose. We found associations (P less than 0.005) between LCAT activity and total cholesterol and between LCAT and free fatty acid levels; the coefficients of negative correlation were 0.543 and 0.607, respectively. Concomitantly to the increment in plasma total cholesterol levels, there was a decrease in the high-density lipoprotein (HDL) cholesterol fraction; the latter, which was 40% of the total plasma cholesterol in control and dextrose-infused rats, declined to 9% in rats given Intralipid. Administration of heparin during Intralipid infusion, even up to 10 IU/ml of TPN, did not affect any of these changes. After dextrose infusion, the values of all three parameters were similar to those of the control group. Plasma lipolytic activity was not significantly different between rats given infusion (Intralipid or dextrose) and controls. However, in the presence of heparin, plasma lipolytic activity increased similarly in both infused groups. These data indicate that in young rats, Intralipid infusion leads to an increase in plasma total cholesterol and free fatty acid levels, which correlates with a decrease in LCAT activity; the concurrent decrease in HDL cholesterol levels might account, in part, for the loss of LCAT activity. The administration of heparin results in an elevation of plasma lipolytic activity; however, it does not prevent the hypercholesterolemia, nor the decline in LCAT activity associated with Intralipid infusion.

Animals↗
PubMed1989

Lipases in human milk: effect of gestational age and length of lactation on enzyme activity.

Human milk contains two lipases, bile salt-stimulated lipase (BSSL) and lipoprotein lipase (LPL). In the mammary gland, LPL provides long-chain fatty acid for milk fat synthesis. LPL has no known function in milk, but has been implicated in milk fat hydrolysis during cold storage. BSSL may have an important role in infant fat digestion. The aims of the present studies were to assess (1) the methodological validity of using whole milk to analyze BSSL activity, (2) the longitudinal variation of BSSL and LPL activity in the milk of mothers delivering premature and full-term infants, and (3) the stability of BSSL and LPL activity during cold storage. Diluted whole milk and purified BSSL were shown to have similar characteristics. LPL activity was equally stable at -20 and -70 degrees C, whereas BSSL activity was higher in milks stored at -70 than at -20 degrees C (38.8 +/- 0.88 vs 33.3 +/- 0.87 U/ml milk, respectively; 1U = 1 mumol free fatty acid release/min). Levels of BSSL activity in preterm and term milk were similar. LPL activity tended to be higher in term milk. Overall, BSSL activity showed significant longitudinal variation, being highest at 1 and 3 weeks of lactation (43.2 +/- 0.04 and 42.6 +/- 1.03 U/ml milk, respectively). For LPL, the longitudinal pattern of activity depended upon the length of pregnancy. Implications for infant nutrition and mammary gland biology are discussed.

Female↗
PubMed1989

Milk composition and volume during the onset of lactation in a diabetic mother.

Milk volume and composition were examined in a diabetic mother on days 3-7 postpartum. By day 5 milk volume produced and concentrations of sodium, potassium, chloride, lactose, protein, calcium, magnesium, and citrate were within limits of a reference population. Fat content of the milk was slightly lower. Free fatty acids were 2% of total lipid on day 3 but increased to 23% on days 4-7, suggesting impaired esterification in the mammary gland. Total milk lipoprotein lipase increased approximately fourfold during days 4-5. Other changes were 1) low cholesterol content, only one-fifth of normal milk; 2) decreased medium-chain fatty acids, suggesting impairment of fatty acid synthesis in the mammary gland; 3) increased oleic acid; and 4) high concentrations of polyunsaturated fatty acids, suggesting increased chain elongation. These results suggest that diabetes produces changes in lipid metabolism in the mammary gland that alter the composition of milk produced by the diabetic mother.

Adult↗
PubMed1989

Effect of activation of central nervous system serotonin 1A receptors on cardiorespiratory function.

Previous studies indicate that the new antihypertensive drug, urapidil, acts at the ventral surface of the medulla in cats to produce a fall in blood pressure. In addition, urapidil was found in receptor binding studies to have a relatively high affinity for the serotonin 1A receptor. These results suggest that drugs which bind to the serotonin 1A receptor might exert hypotensive effects at the ventral surface of the medulla (VSM). To test this hypothesis, the effects of 8-hydroxy-2-(di-N-propylamino)tetralin (8-OH-DPAT), the prototype drug for activating serotonin 1A receptors, were evaluated for cardiovascular activity after local application to the VSM. 8-OH-DPAT applied bilaterally to the intermediate area of the VSM in a dose of 1 micrograms/side produced a decrease in mean blood pressure of 60 +/- 7 mm Hg (P less than .05) and a decrease in heart rate of 26 +/- 4 beats/min (P less than .05) (n = 8). Increases in respiratory rate (8 +/- 1 breaths/1 min) and decreases in tidal volume (13 +/- 4 ml) also occurred. These changes were associated with a significant increase in respiratory minute volume (130 +/- 41 ml, P less than .05). Similar cardiorespiratory changes were produced by application of another drug with high affinity for the serotonin 1A receptor, namely B695-40, to the intermediate area of the VSM. Intravenous administration of 8-OH-DPAT in a dose of 100 micrograms/kg mimicked the cardiorespiratory effects of ventral surface application of this agent.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Importance of central nervous system serotonin-1A receptors for mediating the hypotensive effect of urapidil.

Urapidil is thought to lower blood pressure by both a peripheral and a central mechanism. The former effect is caused by blockade of alpha-1 adrenoceptors whereas the latter effect has been shown to occur in the medulla, specifically at the intermediate area on the ventral surface of the medulla. The receptor mediating the central effect is not the alpha-1 adrenoceptor, but has been postulated to be the serotonin (5-HT)1A receptor. To determine whether urapidil lowers blood pressure by stimulating 5-HT1A receptors at the intermediate area, we applied urapidil bilaterally (50 micrograms/side) to the intermediate area of chloralose-anesthetized cats while monitoring arterial blood pressure and heart rate. Application of urapidil caused decreases in mean blood pressure and heart rate of 66 +/- 8 mm Hg and 31 +/- 7 beats/min, respectively. Pretreatment with the 5-HT1A and 5-HT2 receptor antagonist, spiperone (30 micrograms/side), counteracted the effects of urapidil. Pretreatment with the 5-HT2 receptor antagonist, ketanserin, did not alter the hypotensive effect of urapidil. Urapidil given i.v. in a dose of 2 mg/kg decreased mean blood pressure and heart rate by 53 +/- 6 mm Hg and 10 +/- 2 beats/min, respectively. At the peak of the i.v. response, spiperone (30 micrograms/side) was applied to the intermediate area and increased mean blood pressure and heart rate by 52 +/- 6 mm Hg and 20 +/- 4 beats/min, respectively, thus effectively reversing the effects of i.v. urapidil.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Drug interaction with gamma-aminobutyric acid/benzodiazepine receptors at the ventral surface of the medulla results in pronounced changes in cardiorespiratory activity.

Studies were carried out in chloralose-anesthetized cats while monitoring respiratory (tidal volume and respiratory rate) and cardiovascular (arterial pressure and heart rate) activity. Midazolam applied bilaterally to the intermediate area of the ventral surface of the medulla in doses of 0.75, 7.5 and 75 micrograms/side reduced tidal volume by -6 +/- 3, -10 +/- 1 and -11 +/- 1 ml, respectively. A dose of 250 micrograms/side produced apnea in each animal tested. Corresponding changes in arterial pressure were -35 +/- 9, -44 +/- 6, -43 +/- 9 and -64 +/- 17 mm Hg, respectively. Larger doses of chlordiazepoxide (e.g., 1000 micrograms/side) were required to produce similar effects. Intravenous administration of midazolam in doses of 1.5 to 150 micrograms had no significant effect on cardiorespiratory activity. However, larger doses of midazolam given i.v. produced cardiorespiratory depression that was similar to that observed with centrally applied drug. Pretreatment or treatment with centrally applied flumazenil or bicuculline counteracted the cardiorespiratory effects of centrally applied midazolam. Most importantly, ventral surface application of flumazenil counteracted the cardiorespiratory depressant effects of i.v. midazolam. Central administration of ethyl-beta-carboline-3-carboxylate produced cardiorespiratory effects opposite to those seen with midazolam, and these stimulatory effects were also counteracted by centrally applied flumazenil. These results indicate that alterations in cardiorespiratory activity can be produced by drugs interacting with gamma-aminobutyric acid/benzodiazepine receptors at the ventral surface of the medulla.

Allosteric Regulation↗
PubMed1989

Gastric lipolysis and fat absorption in preterm infants: effect of medium-chain triglyceride or long-chain triglyceride-containing formulas.

The extent of gastric lipolysis, fat absorption, and infant weight gain was studied in 12 preterm infants (gestational age 28.75 +/- 0.50 weeks, postnatal age 6.08 +/- 0.81 weeks) fed medium-chain triglyceride or long-chain triglyceride formula for 1 week in a crossover design. The former formula contained 42% of 8:0 and 10:0 and 19% of 12:0, 14:0, and 16:0; the latter formula contained only 7% of 8:0 and 10:0 and 46% of 12:0, 14:0, and 16:0. Gastric aspirates were obtained on the second and third day of formula feeding for quantitation of lipase activity and of the extent of gastric lipolysis. Fat balance studies were conducted during the last three days of each feeding regimen. The study showed that (1) there was marked hydrolysis of formula fat in the stomach during feeding of either medium-chain triglyceride formula or long-chain triglyceride formula (20% and 16%, respectively); (2) lipase activity in the gastric aspirates was less during feeding of medium-chain triglyceride formula than before the meal, which suggested stimulation of lipase secretion by long-chain fatty acid released from long-chain triglyceride formula fat or more rapid binding of lipase to ingested lipid in the medium-chain triglyceride formula; (3) fatty acid distribution in glycerides and free fatty acids showed preferential release of medium-chain (8:0, 10:0) and long-chain unsaturated (18:1, 18:2) fatty acids in the stomach. The low content of 8:0 and 10:0 in gastric triglyceride and free fatty acids suggested that medium-chain fatty acids were absorbed directly in the stomach.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Weight↗
PubMed1988

Lingual and gastric lipases: species differences in the origin of prepancreatic digestive lipases and in the localization of gastric lipase.

The source of the lipase(s) acting in the stomach was investigated in five animal species: rat, mouse (rodents), rabbit (lagomorphs), guinea pig (caviidae), baboon and human (primates). The activity of lingual and gastric lipases was quantitated in homogenates of lingual serous glands and of gastric mucosa, respectively, by the hydrolysis of tri[3H]oleylglycerol and is expressed in units/g (1 U = 1 mumol [3H]oleic acid released/min) per g tissue wet weight, mean +/- S.E. There were marked differences in the activity level of lingual and gastric lipases among species: mouse and rat had high levels of lingual lipase activity (250 +/- 20 and 824 +/- 224 U/g) and only traces of gastric lipase activity (4.5 +/- 0.9 and 0.04 U/g, respectively), whereas rabbit and guinea pig had no lingual lipase activity and only gastric lipase activity (78 +/- 48 and 27 +/- 7.4 U/g, respectively). In the baboon and human, gastric lipase was the predominant enzyme (109 +/- 20 U/g and 118 +/- 8.8 U/g, respectively), whereas lingual lipase activity was present in trace amounts only (0.04 U/g and 0.3 U/g, respectively). In addition to species differences in the origin of the preduodenal lipases, there were also species differences in the distribution of gastric lipase in the stomach. Thus, while in the rabbit, gastric lipase was localized exclusively in the cardia and body of the stomach, it was diffusely distributed in the entire stomach of the guinea pig and baboon. A comparison between the level of activity of lipase and pepsin (the two chief digestive enzymes secreted by the stomach), showed differences in their localization in the species studied. The difference in source (tongue vs. stomach) and site (cardia-body vs. entire stomach) of lipase secretion must be taken into account in future studies of these digestive enzymes. Although the exact contribution of lingual and gastric lipases individually to fat digestion in species which contain both enzymes cannot yet be evaluated, the markedly higher levels of gastric lipase activity in the baboon and human suggests that, in primates, gastric lipase is probably the major non-pancreatic digestive lipase.

Animals↗
PubMed1988

Gastric lipase: localization in the human stomach.

The aim of this study was to determine the range of activity and the location of lipase in the human stomach. The range of lipase activity in gastric mucosa of surgical specimens from the fundic area of 22 subjects was 594 to 3350 mU [mean, 1598 +/- 144 mU tri[3H]olein, (1 mU-1 nmol [3H]oleic acid released from tri[3H]olein per minute per milligram protein)]. For localization of activity, pinch biopsy specimens of gastric mucosa from 6 subjects were taken from the greater and lesser curvatures within 2 cm of the gastroesophageal junction (upper greater curvature and upper lesser curvature) and within 2 cm of the pylorus (lower greater curvature and lower lesser curvature). Lipase activity was higher in the upper greater curvature (405 +/- 92 mU) than in the upper lesser curvature (32 +/- 13 mU) and lowest in the antral area (16 +/- 9 mU in the lower lesser curvature and 10 +/- 2 mU in the lower greater curvature). The data show that in the human, lipase activity is localized primarily in the fundic area of the stomach. Comparison of the lipase activity levels in the gastric mucosa with lingual lipase activity levels in specimens of lingual serous glands indicates that in humans, gastric lipase is the main lipase active in the stomach.

Adult↗
PubMed1988

Effect of heparin dose and infusion rate on lipid clearance and bilirubin binding in premature infants receiving intravenous fat emulsions.

The effect of heparin dose and infusion rate on plasma lipids, lipases, and unbound bilirubin was investigated in 22 premature infants with physiologic jaundice. Infants were randomly assigned to receive low or high intravenous doses (24 vs 137.3 U/day) of heparin. Each patient then received 2 g/kg/day of 10% Intralipid on 2 successive days: one day during a 15-hour period and the other day over 24 hours, with the order assigned randomly. The results demonstrate a significantly greater change in serum-free fatty acids in infants receiving the high heparin dose during the 15-hour lipid infusion period. Lipoprotein lipase activity rose more with the high heparin dose and equally at either infusion rate. We conclude that lipid infusions of 2 g/kg/day with low heparin dosage infused over 24 hours resulted in less elevation in serum-free fatty acids. There were no adverse effects on unbound bilirubin at either infusion rate or heparin dosage.

Bilirubin↗
PubMed1988

Effect of total parenteral nutrition on lipase activity in the stomach of very low birth weight infants.

Lipase activity was quantitated in gastric aspirates of 7 premature infants (gestational age 24-29 weeks) during periods of total parenteral nutrition (TPN), mixed parenteral nutrition and gavage feeding or exclusive gavage feeding. The infants were studied from birth until the establishment of exclusive gastric gavage feeding. Lipase activity in gastric aspirates (quantitated by the hydrolysis of 3H-triolein at pH 4.2 and expressed in nmol 3H-oleic acid released/min/ml gastric aspirate) did not differ significantly as a function of mode of feeding: 570 +/- 235 during TPN, 260 +/- 145 during mixed parenteral nutrition and gavage feeding, and 374 +/- 149 during exclusive gastric gavage feeding. The data suggest that, contrary to the intestine and pancreas, the digestive function of the stomach is not impaired during TPN in the very preterm infant.

Humans↗
PubMed1988

Low levels of apolipoprotein A1 are not contributors to the low lecithin-cholesterol acyl transferase activity in premature newborn infants.

Umbilical cord sera were obtained from three groups of newborn infants; group I (n = 8) and group II (n = 12) weighed less than 1500 g and between 1500 and 2500 g, respectively. Group III (n = 16) was full term and weighed more than 2500 g. Lecithin-cholesterol acyl transferase activities, determined as the rates of esterification of [3H]cholesterol, were 0.13 +/- 0.01, 0.17 +/- 0.01, and 0.26 +/- 0.01 (mean +/- SEM) nmol/h/ml for groups I, II, and III, respectively. The adult value (n = 8) was 0.96 +/- 0.01 nmol/h/ml. The respective apolipoprotein A1 (apo-A1) levels were 52 +/- 6, 59 +/- 4, and 67 +/- 4 (mean +/- SEM) mg/dl. Serum level of apo-A1 in adults was 137 +/- 6 mg/dl. Plasma high-density lipoprotein cholesterol levels increased with gestational age. However, in newborn infants, high-density lipoprotein apo-lipoprotein B, total cholesterol, and triglyceride levels, were significantly lower than in adults. These data indicate that serum levels of lecithin-cholesterol acyl transferase activity significantly (p less than 0.01) increase whereas the levels of apo-A1 do not significantly change with the gestational age. Also, in full-term newborns, lecithin-cholesterol acyl transferase activity is only 27%, whereas apo-A1 levels are 49% of adult values. Therefore, lower levels of apo-A1 do not account for the significantly lower activity of lecithin-cholesterol acyl transferase in preterm as compared to full-term newborn infants.

Apolipoproteins A↗
PubMed1988

Cardiorespiratory effects produced by activation of cholinergic muscarinic receptors on the ventral surface of the medulla.

Our purpose was to examine the influence of inhibition of cholinesterase at the ventral surface of the medulla on cardiorespiratory activity in the chloralose-anesthetized cat. Administration of the anticholinesterase agent, diisopropylfluorophosphate (DFP) to areas responding to acetylcholine (i.e., rostral and caudal chemosensitive areas of the ventral surface of the medulla) in doses ranging from 12.5 to 50 micrograms bilaterally had minimal effects on cardiorespiratory activity. However, similar doses applied to the intermediate area of the ventral surface of the medulla produced an increase in tidal volume and hypotension. For example, a dose of 12.5 micrograms increased tidal volume by 14 +/- 3 ml (P greater than .05). Similar responses were seen with higher doses of DFP; in addition, respiratory depression (apnea) also occurred. This depression was characterized by a slowing in respiratory rate. The organophosphate compound, soman, in doses of 0.25 and 0.5 micrograms produced effects similar to those seen with DFP with the exception that an increase in respiratory rate was observed before the decrease in respiratory rate occurred. In addition, a greater degree of hypotension was observed with soman as compared to DFP. Findings comparable to those obtained with DFP were produced by the muscarinic receptor agonist, oxotremorine (0.077-10 micrograms). The effects of DFP, soman and oxotremorine were counteracted by locally applied atropine. In addition, measurements of acetylcholinesterase activity taken from the rostral, intermediate and caudal areas indicate a relatively low activity at the rostral area but a relatively high activity at the intermediate area.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Role of nonpancreatic lipolytic activity in exocrine pancreatic insufficiency.

Patients with exocrine pancreatic insufficiency may absorb greater than 50% of dietary fat despite the absence of measurable pancreatic lipase activity. Nonpancreatic lipolytic activity was measured in gastric and duodenal aspirates from 5 patients with exocrine pancreatic insufficiency secondary to alcoholism and in aspirates from 5 alcoholics without evidence of exocrine pancreatic dysfunction (controls). Samples were collected under fasting and postprandial conditions. All patients with exocrine pancreatic insufficiency had nonpancreatic lipolytic activity in gastric and duodenal aspirates. Lipolytic activity in gastric aspirates was not significantly different between the patients with exocrine pancreatic insufficiency and the controls during the fasting and postprandial periods. Pancreatic insufficiency was associated with significantly (p less than 0.05) higher nonpancreatic lipolytic activity in the duodenum under fasting conditions. No significant difference between the groups was found in postprandial nonpancreatic lipolytic activity. Nonpancreatic lipolytic activity accounted for approximately 90% of total lipolytic activity at the ligament of Treitz in patients with exocrine pancreatic insufficiency as opposed to 7% in the control subjects. These observations suggest a significant role for nonpancreatic lipolytic activity (lingual lipase and gastric lipase) in fat digestion in patients with pancreatic insufficiency secondary to chronic alcohol abuse.

Alcoholism↗
PubMed1987

Respiratory depressant effects of GABA alpha- and beta-receptor agonists in the cat.

The aim of this study was to evaluate the cardiorespiratory effects of intravenously administered gamma-aminobutyric acid (GABA) alpha-(4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol, THIP) and beta-(baclofen) receptor agonists and to locate the site of action of these drugs in the brain. THIP and baclofen were administered to alpha-chloralose-anesthetized cats while minute ventilation (VE), arterial blood pressure (AP), and heart rate were monitored. THIP, in doses of 0.5 to 2 mg/kg decreased VE, tidal volume (VT), and AP. No changes in respiratory rate (f) or inspiratory (TI) or expiratory (TE) duration were observed. Baclofen, in doses of 0.5 to 4 mg/kg, decreased VE, f, and AP. VT and TI increased and an "apneustic" breathing pattern was seen. THIP (9.5 micrograms), applied bilaterally to the glycine-sensitive area of the ventral medulla, reproduced the effects seen with intravenous administration. Application of 10 micrograms of bicuculline bilaterally to this area reversed the effects of intravenous THIP but not those of baclofen. Baclofen (5.6-56 micrograms), administered by the intracisternal route, produced the same respiratory effects seen with intravenous administration. We conclude that activation of GABA alpha- and beta-receptors produces cardiorespiratory depression. However, this is accomplished by different mechanisms and by actions exerted at different central nervous system sites.

Animals↗