Biomedical subjects

K Sundaram

Publications and source records attributed to K Sundaram.

At least 19 recordsLinked to original sources

PubMed1995

Feedback regulation of gonadotropins by androgens in rats: is 5 alpha-reduction involved?

The action of testosterone (T) on the sex accessory organs, such as ventral prostate (VP) and seminal vesicles (SV) is amplified by its 5 alpha-reduction to dihydrotestosterone (DHT). This does not happen in the case of muscle (levator ani, LA) which contains little or no 5 alpha-reductase activity. It has been suggested that the regulation of gonadotropins by T may also be mediated by its 5 alpha-reduced metabolites. We investigated this question by utilizing two types of androgens: (1) T and 17 alpha-methyl-testosterone (17MT), whose potency increases following 5 alpha-reduction; and (2) 19-nortestosterone (NT) and 17 alpha-methyl-19-nortestosterone (17MNT) whose potency decreases following 5 alpha-reduction. Castrated rats were used to investigate the ability of these androgens to stimulate VP, and SV (androgenic action) and LA growth (anabolic action) and to suppress the post-castration rise in LH levels. In addition, modification of these actions by a 5 alpha-reductase inhibitor (5 alpha-RI) was studied. Compared to T, NT was approximately 5 times less potent in stimulating VP and SV. By contrast, it was twice as potent as T in stimulating LA growth. Similarly, 17MNT was 5 times less androgenic but twice as anabolic as 17MT. The antigonadotropic potency of both the 19-nor compounds was 2-3 times greater than that of their respective 19-methylated parent compounds. The similarity in their anabolic and antigonadotropic potency suggested that 5 alpha-reduction is not a factor in their antigonadotropic action. This was confirmed by the use of the 5 alpha-RI. Treatment of rats receiving the androgens with 5 alpha-RI showed that it decreases the androgenic activity of T and 17MT while it increases the androgenic activity of NT and 17 MNT. In all cases the anabolic activity and the antigonadotropic potency remained unchanged. It is concluded that the regulation of pituitary gonadotropin secretion by T does not depend upon its 5 alpha-reduction to DHT.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1995

Different patterns of metabolism determine the relative anabolic activity of 19-norandrogens.

Testosterone, the principal androgen secreted by Leydig cells, exerts a wide range of actions including growth of the male reproductive tract (androgenic effects) and growth of non-reproductive tissues such as muscle, kidney, liver, and salivary gland (anabolic effects). As androgenic steroids were discovered some were found to have relatively more anabolic than androgenic activity. The results reviewed in this report suggest that these differences result, in part, from the differential metabolism of the steroids in individual tissues and the varied activities of the individual metabolites. In the accessory sex organs (e.g. the prostate) testosterone is 5 alpha-reduced to dihydrotestosterone (DHT) which, due to its higher affinity for androgen receptors (AR), amplifies the action of testosterone. In contrast, when 19-nortestosterone (NT) is 5 alpha-reduced, its affinity for AR decreases, resulting in a decrease in its androgenic potency. However, their anabolic potency remains unchanged since significant 5 alpha-reduction of the steroids does not occur in the muscle. 7 alpha-methyl-19-nortestosterone (MENT) does not get 5 alpha-reduced due to steric hindrance from the 7 alpha-methyl group. Therefore, the androgenic potency of MENT is not amplified as happens with testosterone. These metabolic differences are responsible for the increased anabolic activity of NT and MENT compared to testosterone. Part of the biological effects of testosterone are mediated by its aromatization to estrogens. The fact that MENT is also aromatized to 7 alpha-methyl estradiol, a potent estrogen, in vitro by human placental and rat ovarian aromatase suggests that some of the anabolic actions of MENT may be mediated by this estrogen.

Anabolic Agents↗

PubMed1995

Mechanism of androgen-induced thymolysis in rats.

To investigate the mechanism of androgen-induced thymolysis, the effects of various androgens, including testosterone (T), 19-nortestosterone, and 7 alpha-methyl-19-nortestosterone (MENT), were compared with those of estradiol and dexamethasone (DEX) in intact, castrated, and adrenalectomized male rats. The potency comparisons on thymus regression, based on mass of steroids, showed DEX to be the most potent, followed by estradiol and the androgens. Among the androgens, MENT was the most potent, followed by nortestosterone and T, an order similar to their anabolic potency on muscle. As the thymolytic effects of T and MENT were not altered by the concomitant administration of an aromatase inhibitor or a 5-reductase inhibitor, it was concluded that the effects of androgens were not mediated by their conversion to estrogens or 5 alpha-reduced metabolites. Involvement of glucocorticoid receptors in androgen action was excluded because mifepristone (an antiglucocorticoid) blocked DEX-induced, but not T- or MENT-induced, thymus regression. Flutamide, an antiandrogen, significantly blocked the thymolytic effect of T and MENT, providing further support for this conclusion. This suggested that the thymolytic action of androgens is an intrinsic property mediated via androgen receptors (AR). The occurrence of AR in the thymus was demonstrated by binding assays and the presence of AR messenger RNA (mRNA) by reverse transcriptase-polymerase chain reaction. Quantitative reverse transcriptase-polymerase chain reaction for AR mRNA in the thymus showed 6-fold more AR mRNA in the thymic epithelial cells than in the thymocytes. However, epithelial cells represent only a small fraction of the thymus. Hence, it is hypothesized that the androgens produce their thymolytic effects by stimulating the secretion of a factor(s) by the thymic epithelial cells that, in turn, causes regression of the thymus.

Adrenalectomy↗

PubMed1994

Aromatization of 7 alpha-methyl-19-nortestosterone by human placental microsomes in vitro.

Part of the biological effects of testosterone (T) are mediated by its enzymatic reduction to 5 alpha-dihydrotestosterone (DHT) or aromatization to estradiol (E2). 7 alpha-Methyl-19-nortestosterone (MENT) is a synthetic androgen that is considerably more potent than T. Previous studies have shown that MENT is not 5 alpha-reduced. The studies reported here were undertaken to determine whether MENT undergoes enzymatic aromatization in vitro. Human placental microsomes were used as the source of the aromatase. Radioactive or nonradioactive T or MENT was incubated with the microsomes in the presence of NADPH and the metabolites extracted out with ethyl ether. Following evaporation of ether, the residue was dissolved in benzene-petroleum ether and extracted with 0.4 N NaOH which selectively removes phenolic metabolites of the androgens. When either radioactive T or MENT was incubated with the aromatase in the presence of NADPH, there was a 20-fold increase in the amount of radioactivity extracted with NaOH. In contrast, if the incubation was carried out in the absence of NADPH or in the presence of R76713, an aromatase inhibitor, most of the radioactivity remained in the benzene-petroleum ether phase. To further identify the enzymatic reaction products, thin layer chromatography (TLC) was performed. The Rf value for MENT was 0.22 while that of the major reaction product was 0.34, which corresponded with the RF value of the estrogen, 7 alpha-methyl-estradiol (MeE2). This was further verified by using a second solvent system for the chromatographic separation. In an effort to ascertain whether the metabolites bind to estrogen receptors (ER), rat uterine cytosol was used. NaOH extracts of medium following incubation of nonradioactive MENT with microsomes showed competitive inhibition of [3H]E2 binding to rat uterine ER. Furthermore, after [3H]MENT was incubated with microsomes, the radioactive metabolite extracted in NaOH showed specific binding to the ER which could readily be displaced with E2 or MeE2. These results indicate that like T, MENT undergoes enzymatic aromatization.

Aromatase↗

PubMed1994

7 alpha-Methyl-19-nortestosterone: an ideal androgen for replacement therapy.

MENT is a synthetic androgen which cannot be 5 alpha-reduced. Therefore, relative to T, its stimulatory action on the prostate is lower than that on the muscle and pituitary. Like T, MENT undergoes enzymatic aromatization to an estrogen. We conclude that the use of MENT instead of T for androgen replacement therapy could have health-promoting effects by reducing the occurrence of prostate disease.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1992

The biological activity of 7 alpha-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone.

Based on the premise that testosterone, but not 7 alpha-methyl-androgens, is reduced at the 5 alpha-position in the prostate and seminal vesicles, the differential bioactivities of these androgens were investigated in castrated rats. The ability of 7 alpha-methyl-19-nortestosterone acetate (MENT) to increase the weights of ventral prostate and seminal vesicles of castrated rats was four times higher than that of testosterone, while its effect on the weights of bulbocavernosus plus levator ani muscles (muscle), was 10 times that of testosterone. MENT was also approximately 12 times more potent than testosterone in the suppression of serum gonadotropin levels. A dose of testosterone that maintains serum gonadotropin levels and muscle mass also maintains prostate and seminal vesicle weights in castrated rats. By contrast, a dose of MENT that maintains muscle and gonadotropins does not maintain prostate and seminal vesicles. The action of other 7 alpha-methylated androgens were similar to that of MENT. The importance of 5 alpha reductase in the differential action of testosterone and MENT on prostate was confirmed by using a 5 alpha-reductase inhibitor. The activity of testosterone was significantly suppressed in the ventral prostate and seminal vesicles but not on muscle by the 5 alpha-reductase inhibitor (N,N-diethyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide). The enzyme inhibitor, however, had no influence on the activity of MENT on either tissue. In contrast, cyproterone acetate, an antiandrogen that competitively binds to the androgen receptors, inhibited the action of MENT and of testosterone on the prostate as well as on the muscle. In conclusion, these observations show that 7 alpha-methylated androgens can maintain muscle mass and normal gonadotropin levels in androgen deficient rats without hyperstimulating the prostate. These findings suggest that 7 alpha-methylated androgens may offer some health benefits to men who require androgen treatment.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed1991

Microinjections of norepinephrine into the intermediolateral cell column of the spinal cord exert excitatory as well as inhibitory effects on the cardiac function.

Cardiac responses to microinjections of norepinephrine (NE) into the intermediolateral column of the spinal cord (IML) at T2 level were studied in pentobarbital-anesthetized, immobilized and artificially ventilated, male Wistar rats. For describing the effects of NE conveniently, the doses of NE were divided into two ranges. The small dose-range consisted of 20 nl volumes of 50, 75 and 100 micromolar (microM) solutions (i.e. 1, 1.5 and 2 pmole in 20 nl, respectively). The larger dose-range consisted of 20 nl volumes of 2.5, 25, 40 and 50 millimolar (mM) solutions (i.e. 0.05, 0.5, 0.8 and 1 nmole in 20 nl, respectively). Injections of small doses of NE (1-2 pmole) into the IML increased heart rate (HR); intravenous injections of these doses did not alter either blood pressure (BP) or HR. Larger doses of NE (0.05-1 nmole) elicited a decrease in HR; intravenous injections of these doses increased HR and BP. Maximum increase in HR was produced by injections of 1.5 pmole of NE into the IML; this effect was blocked by prior injections of prazosin (an alpha 1 adrenergic receptor antagonist; 50 pmole) but not idazoxan (an alpha 2 adrenergic receptor blocker; 10 pmole) into the IML. Maximum decrease in HR was elicited by injections of 0.8 nmole of NE into the IML; this effect was blocked by idazoxan (10 pmole) but not prazosin (50 pmole). Microinjections of idazoxan (10 pmole) alone increased HR while prazosin (50 pmole) alone was ineffective. Intravenous injections of chlorisondamine (a ganglion blocker) blocked the increase in HR elicited by injections of 1.5 pmole of NE into the IML.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMed1991

NMDA receptors in the intermediolateral column of the spinal cord mediate sympathoexcitatory cardiac responses elicited from the ventrolateral medullary pressor area.

Microinjections of L-glutamate into the intermediolateral column of the spinal cord (IML) at T1-T3 produced increases in heart rate (predominantly from the right IML) and myocardial contractility (predominantly from the left IML). Maximum responses were elicited from T2 segment. At this site, microinjections of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), quisqualic acid, kainic acid and N-methyl-D-aspartic acid (NMDA) produced dose-dependent increases in heart rate and contractility which were blocked by kynurenate (a non-selective excitatory amino acid receptor antagonist). D-2-Aminophosphonoheptanoate (DAP-7) blocked the effects of NMDA but not kainic acid, quisqualic acid and AMPA. Bilateral microinjections of kynurenate (2 nmol) and DAP-7 (5 nmol) into the IML at T1-T3 significantly decreased the baseline values for contractility index and blocked the usual increase in contractility induced by unilateral microinjections of L-glutamate (1.77 nmol) into the ventrolateral medullary pressor area (VLPA). These observations suggest that: (1) a tonic excitatory input, involving an NMDA-like amino acid as a transmitter, is present in the IML at T1-T3 and (2) the stimulation of VLPA neurons results in the release of an NMDA-like excitatory amino acid in the IML at this level.

2-Amino-5-phosphonovalerate↗

PubMed1990

Radioimmunoassay of 7 alpha-methyl-19-nortestosterone and investigation of its pharmacokinetics in animals.

A method for the measurement of 7 alpha-methyl-19-nortestosterone (7MENT) in serum/plasma by radioimmunoassay (RIA) is described. The antiserum, raised against 7 alpha-methyl-19-nortestosterone-3-O-oxime-bovine serum albumin, had a low titer (final dilution = 1:4500) and low affinity (Ka = 1.17 x 10(9) l/mol) but showed little or no cross-reactivity with several of the steroids tested. The sensitivity of the RIA was 28.2 pg/ml and the mean recovery of added cold steroid was 86 to 100%. Intra- and inter-assay coefficients of variation ranged from 4.3 to 7.3% and 7.3 to 8.4%, respectively. This RIA was used to follow plasma 7MENT levels after a single i.v. injection of the steroid in rats and rabbits. The metabolic clearance rates (MCR) of 7MENT as determined from the plasma disappearance curve for rats and rabbits were 50 l/day and 336 l/day, respectively. The MCR of 7MENT in rats and rabbits lies in the same range as for testosterone. When compared to other nortestosterone derivatives such as norethisterone, 7MENT is metabolized relatively faster.

Animals↗

PubMed1990

A 90-day subcutaneous toxicity and fertility study of a LHRH antagonist in rats.

[Ac-D2Nal1,4Cl-DPhe2,D3Pal3,Arg5,DGlu6+ ++ (anisole adduct),DAla10]-GnRH (Nal-Glu) is an antagonist of LHRH and has the potential to be utilized as an antigonadal agent. A study was undertaken to evaluate the toxicological effects of Nal-Glu in rats. Nal-Glu, dissolved in 5% mannitol in water containing 9 ml/liter benzyl alcohol, was administered subcutaneously. In subchronic studies, groups of 12 male and 12 female rats received 0, 50, 250, or 1250 micrograms/kg body weight (BW) Nal-Glu for 90 days and were killed on Day 91. Additional groups of male and female rats were given the high dose of Nal-Glu (1250 micrograms/kg BW) or vehicle for either 30 or 90 days. Their fertility was assessed by mating them with normal animals. Unlike some other LHRH antagonists, Nal-Glu exhibited a low potency for causing in vitro histamine release from rat peritoneal mast cells. Furthermore, in acute in vivo studies, Nal-Glu was less active in the induction of peripheral edema. In the subchronic study, all doses of Nal-Glu were well tolerated and there were no apparent systemic toxic effects. The pharmacological effects of Nal-Glu were quite evident, however. Nal-Glu treatment led to a significantly decreased body weight gain in the males and a significantly increased body weight gain in the females. There was a dose-dependent decrease in weights of gonads and reproductive organs in both the sexes. Some of the hematological and serological parameters were significantly different in Nal-Glu-treated animals. However, most of the values were within the normal range and are considered to be of no toxicological significance. Histopathological evaluations were made in the control and high-dose groups only. In the male, a seminiferous tubular degeneration and atrophy of the interstitial cells was seen. The prostate and seminal vesicles were also atrophied and the epididymides were devoid of spermatozoa. In the females, the ovaries and uteri were atrophic. The injection site of Nal-Glu-treated rats had inflammatory changes indicative of a local irritating action of the drug. All other tissues had normal histomorphology. Both male and female rats became infertile when 1250 micrograms/kg Nal-Glu was administered for 30 days. Normal fertility was restored 8 weeks after cessation of 90-day treatment. It is concluded that repeated administration of Nal-Glu leads to reversible infertility in both male and female rats. Although it was irritating at the site of injection. Nal-Glu had no systemic toxicological effects.

Animals↗

PubMed1990

Relative effects of different spinal autonomic nuclei on cardiac sympathoexcitatory function.

Mean arterial pressure and heart rate were monitored in immobilized and artificially ventilated male Wistar rats either anesthetized with pentobarbital or decerebrated at midcollicular level. The rate of increase in the left ventricular pressure was also monitored in order to compute contractility index. L-glutamate (1.77 nmole) was microinjected (10 nl) into the following autonomic nuclei of the spinal cord at C8 to T4 levels: 1) intermediolateral column (IML), 2) n. intercalatus spinalis (IC) and 3) n. intercalatus pars paraependymalis (ICpe); this region is commonly known as the central autonomic area (CA). The site of microinjection was marked by injection of a dye; these studies suggested that microinjections of glutamate into the IML are likely to encompass the neurons in the nucleus (n.) intermediolateralis thoracolumbalis pars principalis (ILp) and n. intermediolateralis thoracolumbalis pars funicularis (ILf). Sympathoexcitatory cardiac responses to glutamate microinjections were elicited from T1 to T3 levels; these responses could not be evoked at C8 and T4 levels. In each of these segments, maximum responses were obtained from the IML while the responses evoked from the IC and the CA were minimal. These results suggest that at T1 to T3 levels of the spinal cord, IML is the main cell group regulating sympathetic cardiac function; CA and IC may play a relatively minor role in this function.

Adrenergic Fibers↗

PubMed1990

Allosensitization induced suppression of various murine tumors: role of non-H-2 antigens in antitumor immunity.

Presence of alloantigens on various murine tumors was tested by tumor rejection in allosensitized Swiss mice. The results indicated the presence of alloantigen on immunogenic tumors like chemically induced fibrosarcoma (FS), ascitic sarcoma 180 (S 180) and immunogenic variant of lymphosarcoma (LS-A) in Swiss mice, while these antigens could not be detected by this procedure on spontaneous lymphosarcoma (LS). Allosensitization with skin graft was found to offer quantitatively higher antitumor resistance than the allosensitization achieved by allogeneic lymphocytes. Antitumor effect was not seen when tumor cells were inoculated earlier than day 3 of grafting. Further, host immunosuppression with whole body irradiation up to day of 3 of skin grafting abrogated the antitumor effect. H-2 compatible and non-H-2 incompatible skin graft sensitization of host could offer resistance against both S 180 and LS-A. Further, tumor immune mice rejected H-2 compatible, non-H-2 incompatible skin graft significantly earlier.

Animals↗

PubMed1989

Microinjections of cholinergic agonists into the intermediolateral cell column of the spinal cord at T1-T3 increase heart rate and contractility.

Cardiovascular responses to the microinjections of cholinergic agonists into the intermediolateral cell column (IML) of the spinal cord at T1-T3 level were studied. Mean arterial pressure (MAP), heart rate (HR), the rate of increase in the left ventricular pressure (dp/dt) and contractility index (CI) were monitored in immobilized and artificially ventilated male Wistar rats either anesthetized with pentobarbital or decerebrated at mid-collicular level. Microinjections (20 nl) of carbachol (110-660 pmol) into the right IML elicited a marked increase in HR and a small increase in CI. A marked increase in the CI with relatively little effect on the HR was observed when carbachol was injected into the left IML. The cardioacceleratory effects of carbachol, but not those of L-glutamate, were blocked by prior microinjections of scopolamine (18 nmol) into the IML. Intravenous injections of chlorisondamine (a ganglion blocker) also blocked these effects of carbachol. Spinal transections at C4 or T6 level did not alter these responses. Microinjections of acetylcholine (0.01-1 nmol) into the right IML also produced tachycardic effects. The responses to acetylcholine were blocked by prior injections of a muscarinic receptor blocker (atropine hemisulfate, 0.2 nmol). Microinjections of a selective M2 muscarinic receptor agonist, cis-methyldioxolane (CD; 0.2-0.8 nmol), but not those of a relatively selective M1 receptor agonist (McN-A343; 2-3 nmol), into the right IML elicited an increase in HR. Previous microinjections of a selective competitive M2 receptor antagonist (AFDX-116; 0.8 nmol), but not those of a potent selective M1 receptor antagonist (pirenzepine; 2 nmol), into the IML blocked the effects of CD. Nicotine (0.25-1 nmol) when injected into the right IML also produced positive chronotropic effects. These responses were blocked by prior microinjections of hexamethonium (5 nmol). The above-mentioned results suggest that cholinoceptive neurons, interneurons or terminals are located in the areas of IML which control cardiac functions. Muscarinic as well as nicotinic receptors are present in this area. Muscarinic receptors are predominantly of the M2 type. The physiological significance of the presence of cholinergic receptors in this area in controlling cardiac functions remains to be established.

Acetylcholine↗

PubMed1989

Cholinergic mechanisms in the ventrolateral medullary depressor area.

Cardiovascular actions of cholinergic agonists in the ventrolateral medullary depressor area (VLDA) were investigated. Microinjections (0.2-1.6 nmol/site) of an M2 muscarinic receptor agonist (cis-methyldioxolane; CD) into the VLDA decreased blood pressure (33-71 mm Hg) and heart rate (11-62 beats/min). Microinjections of AFDX-116 (a specific blocker for M2 receptors), but not those of pirenzepine (a specific blocker for M1 receptors), prevented the depressor responses induced by CD. Unilateral microinjections of CD (0.3 nmol) into the VLDA also elicited depressor and bradycardic effects which were blocked by microinjections of bicuculline methiodide (200 pmol) into the ipsilateral ventrolateral medullary pressor area (VLPA). Bilateral vagotomy did not alter the depressor and bradycardic actions of CD in the VLDA. McN-A343 (2-3 nmol/site), an M1 receptor agonist, failed to evoke any response when microinjected into the VLDA. These results indicate that muscarinic receptors of the M2 type are present in the VLDA. Activation of the latter by cholinergic agonists results in depressor and bradycardic responses. These responses are mediated via the VLPA.

Animals↗

PubMed1989

Electrolytic lesions in the depressor area of the ventrolateral medulla of the rat abolish depressor responses to the aortic nerve stimulation.

The pressor (VLPA) and the depressor (VLDA) areas in the ventrolateral medulla were identified with the microinjections of L-glutamate (1.77 nmol/site) in artificially ventilated, pentobarbital-anesthetized male Wistar rats. Electrical stimulation of the left or right aortic nerve (1-6 V, 10-40 pulses/s, 3 ms) produced usual depressor responses. Electrolytic lesions (2.5 mA for 30 s) were placed bilaterally in the VLDA. Lack of responses to subsequent microinjections of glutamate into the VLDA indicated that the lesions were complete. The function of the VLPA was not compromised because it continued to respond to microinjections of glutamate. Subsequent stimulation of the aortic nerves failed to elicit the usual depressor responses. These results confirm our earlier reports indicating that the VLDA is important in mediating the depressor component of the aortic baroreflex.

Animals↗

PubMed1989

Cardiac responses to the microinjections of excitatory amino acids into the intermediolateral cell column of the rat spinal cord.

Sympathoexcitatory cardiovascular responses to the microinjections of L-glutamate into the intermediolateral cell column (IML) of the upper thoracic cord (C8 to T4) were studied. Mean arterial pressure (MAP), heart rate (HR), the rate of increase in the left ventricular pressure (dP/dt) and contractility index were monitored in immobilized and artificially ventilated male Wistar rats anesthetized with pentobarbital or isoflurane. On the right side, microinjections (10-20 nl) of L-glutamate (0.9-1.77 nmol in 0.9% sodium chloride solution, pH 7.4) into the IML at T2 level produced marked tachycardiac responses with relatively small changes in contractility. On the left side, similar microinjections produced marked increase in dP/dt and contractility index with relatively small increase in HR. On either side, the responses were smaller at T1 and T3 level and absent at C8 and T4 level. No changes in blood pressure were observed with microinjections of L-glutamate on either side. Microinjections of N-methyl-D-aspartic acid (NMDA), 1-100 pmol, into the IML elicited responses similar to those of L-glutamate. These amino acids failed to evoke any response when microinjected into the adjacent areas (e.g. 0.5 mm lateral or medial to the IML). The effects of glutamate and NMDA in the IML were blocked by microinjections of glutamic acid diethylester (GDEE) and D-2-amino-7-phosphonoheptanoic acid (D-AP7), respectively. Control microinjections of physiological saline into the IML produced no responses. These results indicate that excitatory amino acids, in small doses and volumes, can be used to identify cardiac sympathoexcitatory neuronal pools in the IML. This preparation may prove useful in characterizing pharmacological actions of various putative neurotransmitters in this region of the spinal cord.

Animals↗

PubMed1989

M2 muscarinic receptor agonists produce hypotension and bradycardia when injected into the nucleus tractus solitarii.

Bilateral microinjections (0.2-2 nmol/site) of a potent M2 muscarinic receptor agonist, cis-methyldioxolane (CD), but not those of a relatively selective M1 receptor agonist (McN-A343; 3 nmol/site), into the intermediate portion of nucleus tractus solitarii (NTS) of pentobarbital-anesthetized rats elicited a decrease in blood pressure (23-52 mm Hg) and heart rate (16-50 bpm). Previous microinjections of a selective competitive M2 receptor antagonist (AFDX-116; 0.8 nmol/site), but not those of a potent selective M1 receptor antagonist (pirenzepine; 2 nmol/site), into the NTS blocked the effects of CD. These results indicate that the muscarinic receptors in the intermediate portion of NTS are of M2 type.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

PubMed1989

Radium-226 retention in placenta and whole body of rat. Preliminary studies.

The 226Ra retention in the placenta of rat during 3 successive pregnancies (92-213 days after injection) was about 4-5 x 10(-3)% of the injected dose (ID) constituting nearly 0.009% of the whole body 226Ra content (45-55% ID) in each pregnancy. Thus a uniform relationship was being displayed between the two contents to a reasonable extent. The implication of this observation is discussed vis-a-vis the determination of Ra body burden.

Animals↗