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Biomedical subjects

M S Manku

Publications and source records attributed to M S Manku.

At least 127 records · Page 7Linked to original sources
PubMed1976

Chloroquine, quinine, procaine, quinidine, tricyclic antidepressants, and methylxanthines as prostaglandin agonists and antagonists.

Chloroquine, quanine, procaine, quinidine, clomipramine, theophylline, and caffeine have been shown to be strong prostaglandin antagonists and weak agonists. The antagonist effect is clearly demonstrable at concentrations reached in human plasma when the drugs are used therapeutically. This suggests that prostaglandins are important in several situations in which their role has hitherto been unsuspected. New approaches to the development of prostaglandin antagonists and new uses for established drugs are indicated. In a preliminary study chloroquine has been successfully used to close patent ductus arteriosus in three infants.

Antidepressive Agents, Tricyclic↗
PubMed1976

Indomethacin inhibits responses to all vasoconstrictors in the rat mesenteric vascular bed: restoration of responses by prostaglandin E2.

Indomethacin added to the perfusing buffer inhibited pressor responses to noradrenaline, angiotensin II, arginine vasopressin, histamine, serotonin, calcium ions and potassium ions in the male rat mesenteric vascular bed. For every pressor agent the indomethacin concentration which inhibited response amplitude by 50% was about 7 microg/ml (2.1 X 10(-5) M). With every pressor agent, prostaglandin (PG) E2 could restore normal responsiveness in indomethacin-blocked preparations even while the indomethacin was still present in the buffer. The concentration of PGE2 required was proportional to the concentration of indomethacin. Preparations completely inhibited by indomethacin needed about 5ng/ml PGE2 for complete restoration of normal responses. Aspirin and mefenamic acid could also inhibit responses to all pressor agents tested but with these drugs only a partial restoration could be achieved by PGE2.

Angiotensin II↗
PubMed1976

Chloroquine, quinine, procaine, quinidine and clomipramine are prostaglandin agonists and antagonists.

Chloroquine, quinine, procaine, quinidine and clomipramine behave as prostaglandin (PG) antagonists in a rat mesenteric vascular bed preparation. The ID50 concentrations were within the range of therapeutically effective human plasma levels in each case. Antagonism to PGE2 was studied in detail and seemed to be at least in part competitive. The drugs also antagonized the effects of PGs A1, A2, F2alpha and E1. Each drug also had weak prostaglandin agonist activity but only over a very narrow range of concentrations. It is possible that some of the clinical actions of these drugs may depend on blockade or imitation of natural PG effects. The findings suggest new approaches to the search for PG antagonists, a new screening technique for anti-inflammatory drugs and possible new uses for these established drugs. A preliminary study suggests that chloroquine may be successful in closing a patent ductus arteriosus in infants.

Animals↗
PubMed1976

Vascular actions of frusemide and bumetanide on the rat superior mesenteric vascular bed: interactions with prostaglandins.

1. The addition of frusemide or bumetanide to perfusion fluid inhibited the response of the isolated mesenteric vascular bed to noradrenaline. 2. Addition of prostaglandin E2 to the perfusion fluid completely restored the response to noradrenaline. 3. Inhibition of prostaglandin secretion by indomethacin with restoration of responses to noradrenaline by the addition of exogenous prostaglandin E2 prevented the inhibitory effect of frusemide or bumetanide on responses to noradrenaline. 4. The inhibitory effects of diuretics on responsiveness to noradrenaline is mediated by blockade of endogenous prostaglandin synthesis.

Animals↗
PubMed1976

Vascular actions of furosemide and bumetanide on the rat superior mesenteric vascular bed: interactions with prolactin and prostaglandins.

The mesenteric vascular bed of the rat was used to investigate the effects of furosemide, bumetanide, prolactin, aspirin, indomethacin and prostaglandin E2 on the pressor response to norepinephrine. Furosemide, bumetanied and indomethacin could all inhibit the responses to norepinephrine: in each case responsiveness was restored by the addition of prostaglandin E2 to the perfusate. Bumetanide and furosemide both failed to inhibit responsiveness in the presence of an adequate amount (50 pg/ml) of prostaglandin E2. As has been shown previously, ovine prolactin in a concentration of 50 ng/ml enhanced pressor responses to norepinephrine while 500 ng/ml, after an initial potentiation, inhibited responsiveness. Aspirin, furosemide and bumetanide all reversed both the potentiation produced by the lower prolactin concentration and the inhibition produced by the higher one. When taken in conjunction with other evidence these results suggest that the diuretics exert their vascular effects by inhibiting prostaglandin synthesis whereas prolactin acts by stimulating such synthesis.

Animals↗
PubMed1976

Physiological cortisol levels block the inhibition of vascular reactivity produced by prolactin.

Cortisol in concentrations similar to the unbound levels of the hormone in human plasma can reverse the inhibition of vascular reactivity produced by prolactin. In the rat mesenteric vascular bed, cortisol alone in similar concentrations had no significant effect on the pressor responses to norepinephrine: the action of cortisol was seen only when prolactin was present. The relationships between the effects of different concentrations of prolactin and cortisol suggest that at some point there is a competitive interplay between the effects of the two hormones. There is indirect evidence that this interplay is at the level of prostaglandin synthesis or release. We suggest that cortisol has no effect on basal prostaglandin production but blocks the synthesis or release occurring in response to polypeptide hormone stimulation.

Animals↗
PubMed1975

Seasonal and sexual variations in the responsiveness of rabbit hearts to prolactin.

Rabbit hearts perfused by the Langendorff technique were studied. The addition of ovine prolactin (NIH-P-S-10) to the perfusate in a concentration of 50 ng/ml produced rapid increases in both the amplitude and rate of contraction in 33 adult male hearts studied in winter. Prepubertal male animals showed no response, and only 1 out of 12 adult females responded. Pretreatment for 10 days with 2.5 mg/day testosterone propionate led to minimal inotropic but not chronotropic responses in 2 out of 4 prepubertal males and 2 out of 4 adult females to prolactin. Clear responses to prolactin were seen in 5 adult males pretreated with reserpine. Propanolol consistently reversed both the inotropic and chronotropic actions of prolactin. The original experiments were performed in January and February. When tested in May, adult males failed to respond to prolactin and this situation, persisted until October when responsiveness again appeared. The same prolactin preparation and procedures were used throughout indicating that the changes must have been due to seasonal variations in the cardiac responsiveness to the hormone.

Animals↗