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Biomedical subjects

I M Khan

Publications and source records attributed to I M Khan.

30 records · Page 2Linked to original sources
PubMed1994

Cardiovascular and behavioral responses to nicotinic agents administered intrathecally.

We have examined the role of the spinal nicotinic receptors in mediating cardiovascular and behavioral responses in conscious rats. Intrathecal administration of nicotinic agonists to the lumbosacral region of the spinal cord caused a dose-dependent increase in systolic blood pressure, heart rate and a nociceptive (behavioral) response. The order of potencies for the pressor response was l-nicotine > or = cytisine > N-methylcarbamylcholine > or = dimethylphenylpiperazinium > d-nicotine. However, cytisine was the most potent in producing the heart rate increase and nociceptive response. Unlike the other agonists, cytisine also exhibited marked desensitization of the three responses upon repeated administration. The effects of nicotine were antagonized in a dose-dependent fashion by mecamylamine, hexamethonium, alpha-lobeline, dihydro-beta-erythroidine and methyllycaconitine. By contrast, cytisine-induced responses were blocked effectively by mecamylamine and methyllycaconitine, but not by alpha-lobeline or dihydro-beta-erythroidine. However, when alpha-lobeline or dihydro-beta-erythroidine antagonism of the pressor response to cytisine was monitored during the initial minute following intrathecal administration, both antagonists significantly inhibited the response. The competitive ganglionic blocker, trimethaphan, or the elapid alpha-toxin, alpha-bungarotoxin, when administered intrathecally, had no effect on nicotine- or cytisine-elicited responses. The cardiovascular responses to intrathecal nicotine and cytisine have two components. The first is likely mediated through direct sympathetic output and desensitizes rapidly to cytisine, the second is coupled indirectly to the nociceptive response and shows a diminished capacity for rapid desensitization. Agonist and antagonist specificities indicate that the spinal nicotinic receptor differs from those in ganglia and those characterized in brain to date. Although antagonist specificity of the blockade of nicotine and cytisine elicited responses differ, this may be due to the unique desensitization capacity of cytisine rather than an action mediated by distinct receptor subtypes.

Aconitine↗
PubMed1994

Ligand specificity of nicotinic acetylcholine receptors in rat spinal cord: studies with nicotine and cytisine.

Administration of nicotinic agonists to the spinal cord leads to a variety of cardiovascular and behavioral responses. The discrete localization of afferent and efferent fibers presents a system in which occupation of nicotinic receptor subtypes might be correlated with specific pharmacologic responses. To this end, we examined [3H]cytisine and [3H]nicotine binding to membranes isolated from regions of the rat spinal cord. [3H]Cytisine showed saturable, noncooperative (nH congruent to 1) binding to a single-class of sites with a Kd of 0.44 +/- 0.01 nM and total saturable sites of 19.9 +/- 0.9 fmol/mg of protein. [3H]Cytisine binding to membranes from intermediolateral cell column and dorsal and ventral sections of the lumbosacral regions each revealed a single class of binding sites with virtually identical Kd values. However, the dorsal sections of the lumbar spinal cord contained a higher number of total binding sites than ventral lumbar or intermediolateral sections. The rank order potencies of the nicotinic agonists competing for [3H]cytisine binding was cytisine > I-nicotine > N-methylcarbamylcholine > dimethylphenylpiperazinium > acetylcholine > d-nicotine > carbamylcholine. Competitive antagonists also competed with high affinities (Ki as low as nanomolar) with the order of potencies being alpha-lobeline > or = dihydro-beta-erythroidine >> methyllycaconitine, whereas the channel blockers, mecamylamine and hexamethonium, only competed at concentrations > or = 100 microM. Competitive ganglionic blockers such as d-tubocurarine or trimethaphan and neurotoxins such as alpha-bungarotoxin, alpha-cobratoxin or neuronal bungarotoxin had weak affinities for cytisine sites. Similar to [3H]cytisine, [3H]nicotine also revealed a saturable single class of binding sites, but of lower affinity. The rank order of Ki values of the agonists, antagonists and neurotoxins for competing with [3H]nicotine binding was similar to the order for [3H]cytisine. Nicotinic receptors in the spinal cord membrane show a specificity for both agonists and antagonists that differ from neuronal receptors in the ganglia or the regions of the brain characterized to date. These findings, when correlated with the pharmacological responses documented in the comparison article suggests that the spinal nicotinic receptors may define a new member of the neuronal nicotinic receptor family.

Alkaloids↗
PubMed1993

Cerebrospinal fluid kallikrein in spontaneously hypertensive and desoxycorticosterone acetate-salt hypertensive rats.

OBJECTIVE: To determine whether immunoreactive tissue kallikrein levels in cerebrospinal fluid (CSF) of spontaneously hypertensive rats (SHR) and desoxycorticosterone acetate (DOCA)--salt-treated hypertensive rats are elevated compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats. DESIGN: The present study was designed to test the hypothesis that the activity of the brain tissue kallikrein-kinin system is enhanced in hypertensive states. METHODS: Age-matched 18- to 19-week-old SHR and WKY rats, and Sprague-Dawley rats treated for 6 weeks either with 2 mg/kg per day DOCA subcutaneously and 0.9% saline in the drinking water, or with vehicle and tap water to drink, were studied. CSF was collected from a cannula inserted into the cisterna magna, and was frozen until the tissue kallikrein in the samples was measured by radioimmunoassay. Arterial pressure in the SHR and WKY rats was measured directly via a cannula inserted in the femoral artery or by tail-cuff plethysmography. RESULTS: In adult 18- to 19-week-old SHR the CSF kallikrein concentration was higher than in WKY rats. The CSF flow rate in SHR was also higher than in WKY rats. The rate of appearance of kallikrein in the CSF of SHR was twice that in WKY rats. Moreover, CSF kininogenase activity in SHR was significantly higher than that in age-matched WKY rats. In DOCA--salt hypertensive rats the CSF kallikrein concentration was higher than in vehicle-treated control rats. Acute elevation of blood pressure with a 120-min intravenous phenylephrine infusion did not change the CSF kallikrein concentration in 50 rats compared with vehicle-treated control rats. This is the first study to quantitate immunoreactive tissue kallikrein in the CSF of rats and to show elevated levels of CSF kallikrein in hypertensive rats compared with normotensive rats. CONCLUSION: The present data suggest that higher brain kallikrein activity in hypertensive rats may play a role in the development of elevated blood pressure.

Animals↗
PubMed1988

Preparation of human cord sera for enzymatic triglyceride assays: removal of free glycerol by ultrafiltration.

Enzymatic triglyceride assays that generate glycerol from triglycerides as a part of the enzymatic process in quantitating serum triglyceride levels give elevated values when external free glycerol is present. Our objective was to develop an ultrafiltration technique that would remove exogenous and/or endogenous free glycerol from small aliquots of human cord sera so that accurate serum triglyceride values could be obtained with the commercially available triglyceride assay kits. Exogenous glycerol was completely removed from cord sera when the samples were washed twice with saline in Amicon Centricon-30 microconcentrators. This ultrafiltration technique lowered cord serum triglyceride levels significantly (P less than 0.001), but had no effect on cord total serum cholesterol levels. A comparison of washed and unwashed cord sera by either polyacrylamide or agarose gel electrophoresis indicated that the serum protein and lipoprotein profiles were not altered by the ultrafiltration process.

Cholesterol↗
PubMed1986

Adenylate cyclase activity of the corpus luteum during the oestrous cycle of the pig.

Basal adenylate cyclase values for corpora lutea (CL) removed from cyclic gilts on Days 3, 8, 13 and 18 were 178 +/- 61, 450 +/- 46, 220 +/- 25 and 208 +/- 18 pmol cAMP formed/min/mg protein, respectively. Basal activity was significantly elevated on Day 8 (P less than 0.001). LH-stimulatable adenylate cyclase values for CL from Days 3, 8, 13 and 18 were 242 +/- 83, 598 +/- 84, 261 +/- 27 and 205 +/- 17 pmol cAMP formed/min/mg protein respectively. Serum progesterone concentrations of 12 gilts bled every 2 days through one complete oestrous cycle ranged from 1.1 to 26.9 ng/ml with highest values between Days 8 and 12. The decline in serum progesterone concentrations was coincident with the decrease in basal adenylate cyclase activity. There was no LH-stimulatable adenylate cyclase activity present in the CL at the specific times of the oestrous cycle examined. We conclude that progesterone secretion by the pig CL is apparently dependent on basal activity of adenylate cyclase.

Adenylyl Cyclases↗
PubMed1976

Bovine pancreatic lipase.I.Isolation, homogeneity, and characterization.

Bovine pancreatic lipase was isolated in pure form by lyophilization of fresh bovine pancreas, extraction of the enzyme with sucrose solution, fractional precipitation with ammonium sulfate and acetone, followed by chromatography on Sephadex G-100. The specific activity of the purest lipase fraction was 1750 micromoles fatty acid, liberated in 30 min per milligram of protein, indicating a purification of approximately 473-fold, with an overall yield of about 42%. Homogeneity of the enzyme was confirmed by rechromatography on Sephadex G-100 as well as with the gel electrophoretic and ultracentrifugal techniques. The purified enzyme gave a typical protein ultraviolet absorption spectrum with maximum absorption at 276 nm and minimum at 252 nm. The purified enzyme exhibited a single pH optimum of 8.8 and an isoelectric point near pH 5.5. Its optimum temperature was 37 C, and its optimum substrate concentration was 10%. These properties resembled those of milk lipase.

Animals↗
PubMed1976

Bovine pancreatic lipase. II. Stability and effect of activators and inhibitors.

Purified bovine pancreatic lipase was highly unstable at and above refrigeration temperature. However, it could be stored frozen without loss of activity. Milk solids had some protective effect upon the enzyme against gamma-irradiation. Low concentrations of sodium, calcium, and magnesium salts stimulated lipolytic activity. However, heavy metal salts, such as ferric, cupric, and mercuric chlorides, were highly inhibitory. The bovine pancreatic lipase appeared to contain sulfhydryl groups which may be essential for the lipolytic activity since p-chloromercuribenzoate, N-ethylmaleimide, sodium arsenite, and iodoacetate inhibited the enzyme. A comparison of bovine pancreatic lipase and milk lipase revealed that the two enzymes were similar in thermal stability and effect of some of the activators and inhibitors on lipolytic activity.

Animals↗
PubMed1976

Bovine pancreatic lipase. III. Lipolysis of oils and fats and fatty acid specificity.

Purified bovine pancreatic lipase hydrolyzed butteroil, vegetable oils, and synthetic glycerides. The enzyme hydrolyzed triglycerides more rapidly than di- and monoglycerides and tripropionin faster than any other synthetic glyceride. Triacetin was the least hydrolyzed glyceride. Gas-liquid chromatographic analysis of the free fatty acids liberated by the lipase from milk fat indicated that the enzyme selectively liberated butyric acid in higher proportion than the relative amount originally in the fat. The enzyme released saturated as well as unsaturated fatty acids from commericial vegetable oils. With regard to the lipolytic behavior, in general, the bovine pancreatic lipase closely resembled milk lipase.

Animals↗