The glucose dependence of pancreatic endocrine responses to 2-deoxyglucose in the calf

Summary The initial plasma glucose concentration of unanesthetized calves with cut splanchnic nerves, given 2-deoxyglucose (1.2 mmoles/kg, i.v.), was either lowered by prior starvation, or raised by a continuous infusion of exogenous glucose. Raising the initial plasma glucose concentration completely suppressed the release of pancreatic glucagon and pancreatic polypeptide but substantially enhanced the release of insulin in response to 2-deoxyglucose.This work has been supported by the Medical Research Council and the Leverhulme Trust. We are also indebted to Mr P.M.M. Bircham and Mr G.P. Macgregor for their skilled technical assistance.     

Modification of the effect of cardio-accelerator nerve stimulation in dogs by clonidine and several alpha-adrenolytics]

In dogs anaesthetized with pentobarbital (30 mg. kg -1 i.v.), clonidine (0,01 mg.kg-1 i.v.) reduced the tachycardia induced at low frequencies by stimulation of the cardiac nerve. The effects of some alpha-adrenoceptor blocking agents on this effect have been studied. Small doses of yohimbine (0.3 mg. kg-1 i.v.) or piperoxan (0.3 mg. kg-1 i.v.) increased the effects of the stimulation and in addition antagonized the inhibitory effects of clonidine and reversed the pressor response to adrenaline. Thymoxamine (1 mg.kg-1 i.v.) and prazosin (1 mg.kg-1 i.v.) did not increase the effect of the stimulation of the cardiac nerve, but reduced the effect of clonidine. ARC239 (0.05 mg.kg-1) reversed the pressor response to adrenaline but even at high doses did not increase the effects of the stimulation of the cardiac nerve or the effects of clonidine. These observations afford further evidence for a dissimilarity between pre and post-synaptic alpha-adrenoceptors.     

Action of N-butylnorsympathone on the effects of cardioaccelerator nerve stimulation in the dog]

In Dogs anaesthetized with pentobarbital (30 mg . kg-1), N-butylnorsympathone (20 mg . kg-1 i.v.) reduced the bradycardia induced by stimulating the cardiac nerve (1, 2, 5, 10 Hz). Phentolamine (1 mg . kg-1 i.v.) or yohimbine (0.3 mg . kg-1 i.v.), two potent alpha-adrenoceptor blocking agents known to block presynaptic alpha-adrenoceptor induced a recovery of the effect of cardiac nerve stimulation. Prazosine (0.050 mg . kg-1 i.v.) an alpha-adrenoceptor blocking agent known to be ineffective on presynaptic alpha-adrenoceptors did not induce a recovery. However neither phentolamine or yohimbine were able to prevent the effects of N-butylnorsympathone. Neither haloperidol (0.050 to 2 mg . kg-1 i.v.) or pimozide (0.20 to 1 mg . kg-1 i.v.) induced a recovery or prevented the effects of N-butylnorsympathone. These results suggest that N-butylnorsympathone may stimulate presynaptic receptors which do not resemble classical presynaptic alpha-adrenoceptors or dopamine receptors.     

Stimulierung der Atmung durch Bradykinin und Kallidin

Summary In guinea pigs and rabbits small doses of bradykinin and kallidin (1–8 µg/kg i.v.), which have no bronchoconstrictor effect, stimulate respiration causing tachy- and hyperpnea. Bilateral vagotomy as well as salicylates (4–40 mg/kg i.v.) abolish these respiratory responses.     

Reversal of net secretion to net absorption of potassium in rat large intestine by dietary potassium depletion

Summary Feeding rats a diet low in potassium and high in sodium for 2 weeks led to a reversal of net potassium secretion to net potassium absorption in ligated segments of distal large intestine (colon descendens and rectum) under in-vivo conditions. This change in the direction of net potassium transport is probably important for the maintenance of potassium homeostasis.The technical assistance of Mrs U. Seeliger is gratefully acknowledged.     

High potassium intake increases the plasma concentration and urinary excretion of vasopressin in the rat

Summary The effect of alterations of dietary potassium intake on the plasma concentration and the urinary excretion of vasopressin was studied in male rats. Ingestion of a high potassium diet resulted in increases in the plasma concentrations of potassium and vasopressin, systolic blood pressure, urine flow, and urinary vasopressin excretion. Ingestion of a low potassium diet had little effect on the plasma vasopressin concentration and systolic blood pressure but caused decreases in the plasma potassium concentration and urinary vasopressin excretion. The results indicate that physiological changes in the plasma potassium concentration or some other consequence of altered dietary potassium intake can affect vasopressin release and excretion.     

Effect of hyperkalemia on insulin secretion

Summary The effect of hyperkalemia on insulin secretion remains undefined. We evaluated portal and peripheral insulin levels in anesthetized dogs after infusions of KCl. The mean maximal increase in peripheral plasma potassium at infusion rates of 0.2 mEq/kg/h was 0.68±0.20 mEq/l. There were no significant increases in either portal or peripheral insulin levels. In contrast, in six dogs whose plasma potassium concentration increased in each case by more than 2.0 mEq/l (infusion rate of 0.5 mEq/kg/h), portal insulin levels increased fivefold (p<0.05). We conclude that only marked increases in plasma potassium concentration stimulate pancreatic insulin secretion.     

Bioavailability of progesterone enhanced by intranasal spraying

Summary The bioavailability of progesterone (P) in terms of area under time-concentration curve and maximal concentration in the serum and cerebrospinal fluid was studied in adult ovariectomized rhesus monkeys following the administration of P as a nasal spray, i.v. or i.m. injections, nasal or eye drops. The bioavailability of P in both the body fluids was found to be considerably higher following its being sprayed intranasally.This work was supported by the World Health Organization, Geneva.     

Identification of mucondialdehyde as a novel stress metabolite

In a survey of antifungal stress compounds induced by cupric chloride we found that leaves ofChenopodium album exuded a highly fungitoxic metabolite mucondialdehyde (trans-2,trans-4-hexadienedial), which was associated with 13-oxo-9,11-tridecadienoic acids (cis-9,trans-11 andtrans-9,trans-11 isomers) presumably resulting from -scission of 13-hydroperoxy-octadecadi(tri)enoic acid. The biogenesis and role as a general defensive agent in plants are briefly discussed.     

Nest cell lining of the solitary beeHylaeus bisinuatus (Hymenoptera: Colletidae)

The nest cell lining ofHylaeus bisinuatus (Hymenoptera: Colletidae) was shown by high-resolution solidstate [¹³C]NMR to be composed of lipid polymer and protein. The lipid polymer was shown by reduction and subsequent GC/MS analysis to be comprised of -hydroxy fatty acids (C₂₀, C₂₂, C₂₄ and C₂₆) and fatty alcohols (C₁₆ to C₃₀). The protein portion of the lining had a silk-like amino acid composition.     

Effect of methyl ester of aristolic acid fromAristolochia indica Linn. on fertility of female mice

Summary Methyl ester of aristolic acid, a pure compound isolated from the roots ofAristolochia indica (Linn.), was found to exert 100% abortifacient activity at a single oral dose of 60 mg/kg b. wt when administered on 6th or 7th day of pregnancy; 20 and 25% abortifacient effect were observed at the same dose on day 10 and 12, respectively.The authors wish to thank Dr S.C. Pakrashi and his associate Mr P.P. Ghosh Dastidar for the compound. Thanks are also due to the Director General of Indian Council of Medical Research for granting a fellowship to one of them (C.S.).     

The effect of a phorbol ester upon the cholinergic regulation of potassium permeability in the rat submandibular gland

Acetylcholine releases calcium from cytoplasmic stores and permits an influx of calcium in salivary acinar cells. The resultant rise in [Ca²⁺]_i causes an increase in potassium permeability which is an important part of the secretory response. We have investigated the effects of 12-0-tetradecanoyl phorbol-13-acetate, a potent activator of protein kinase C, upon this regulation of potassium permeability in superfused pieces of rat submandibular salivary gland. This compound inhibited the initial [Ca²⁺]_o-independent component of the response of acetylcholine but had no effect upon the subsequent [Ca²⁺]_o-dependent phase. This compound does not, therefore, appear to inhibit receptor-regulated calcium influx.     

Short-term effects of colcemid on the rapid axonal transport of proteins in the optic pathway of chick embryos

Riassunto La somministrazione endoculare di piccole dosi di Colcemid in embrioni di pollo al 13° e al 18° giorno di incubazione diminuisce la sintesi proteica nella retina. Pur in misura diversa, i due farmaci bloccano il trasporto assonico di proteine dalle cellule gangliari retiniche al tetto ottico. Anche nell'embrione quindi il trasporto assonico dipende dalla integrità dei microtubuli neuronali.

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This work was supported by Consiglio Nazionale delle Ricerche (C.N.R.), Rome, Italy.     

Lack of pyrogenic tolerance transmission between brain and periphery in the rabbit

Summary Successive injections of lipopolysaccharide (LPS) either intravenously (i.v.) or intracerebroventricularly (i.c.v.) induced pyrogenic tolerance to LPS in rabbits. Tolerance was shown by a decrease of the magnitude of the fever response to repeated doses of LPS, irrespective of the route of pyrogen administration. A significantly greater and more dramatic decrease of the fever index, however, was observed in rabbits made tolerant to pyrogen given i.v. than when the pyrogen was given i.c.v. Transmission of the pyrogenic toleraance between brain and peripheral tissues, however, has not been ascertained.     

Lack of pyrogenic tolerance transmission between brain and periphery in the rabbit

Successive injections of lipopolysaccharide (LPS) either intravenously (i.v.) or intracerebroventricularly (i.c.v.) induced pyrogenic tolerance to LPS in rabbits. Tolerance was shown by a decrease of the magnitude of the fever response to repeated doses of LPS, irrespective of the route of pyrogen administration. A significantly greater and more dramatic decrease of the fever index, however, was observed in rabbits made tolerant to pyrogen given i.v. than when the pyrogen was given i.c.v. Transmission of the pyrogenic tolerance between brain and peripheral tissues, however, has not been ascertained.     

4-Aminopyridine and barium chloride attenuate the anti-epileptic effect of carbamazepine in hippocampal slices

Summary The exact mode of action of the anti-epileptic agent carbamazepine is unknown. In hippocampal slices in which epileptiform discharges were induced by addition of penicillin to the perfusion medium, the depressant effect of carbamazepine was attenuated by the potassium-channel blockers barium chloride (0.1 mM) and 4-aminopyridine (200 M), which suggested that potassium fluxes might be involved in the mechanism of action of carbamazepine.     

Inhibitory effect of ouabain on in vitro and in vivo gastric acid secretion in the frog and the rat

The in vitro and in vivo effects of ouabain on gastric acid secretion in the frog and the rat, the 2 species known to have different sensitivity to ouabain, were studied. It was found that ouabain was a potent inhibitor of histamine-stimulated acid secretion in the isolated frog gastric mucosa. Ouabain administered i.v. at dose levels far below the lethal range also produced a marked and significant reduction of histamine-stimulated gastric acid secretion in the anesthetized frogs and rats. It is considered that the inhibitory effect of ouabain on acid secretion could be partly related to its specific antagonizing action on the Na+ -K+ -ATPase in the gastric mucosa.     

Studies on chemically induced tumors in rats: I. Heterogeneity of tumor cells and establishment of syngeneic, tumor-specific cytotoxic T cell clones

Sarcoma P1 was induced in DA rats by DMBA. Anti-P1 antibodies were produced in DA rats, purified via fixed tumor cells and used to induce anti-idiotypic antibodies in syngeneic rats. The anti-idiotypic antibodies were used to generate cytotoxic, P1 specific DA T cells in vitro. These cytotoxic T cells and P1 tumor cells were cloned by limiting dilution. Using the DA anti-P1 specific cytotoxic T cell clones, we were able to characterize 2 types of P1 tumor cell clones, namely those which were susceptible and those which were resistant to the P1 specific cytotoxic T cells. Cytotoxic T cell injected i.v. into syngeneic DA rats could not prevent the development of lethal P1 tumors.     

The effect of endotoxin on plasma α-aminoisobutyric acid

Summary The i.v. injection of bacterial endotoxin into dogs was found to cause a rapid increase in plasma levels of infused -aminoisobutyric acid. The findings suggest that nonmetabolic factors (tissue uptake, fluid shifts) influence amino acid distribution during endotoxemia.This investigation was supported in part by the Office of Naval Research, Contract N0001476CO132. R.E.K., Postdoctoral Fellow, supported by HL07090. Address correspondence to J.J.S.     

Effects of angiotensin II and of an angiotensin II receptor antagonist on Simian virus 40-induced tumor growth in vivo

Summary The effects of angiotensin II and of the competitive angiotensin II receptor antagonist saralasin on in vivo tumor growth were investigated in hamsters. Angiotensin II strongly inhibited tumor growth while saralasin stimulated it, though the high dose used had partial agonistic angiotensin II-like actions. Lower doses of saralasin were without significant effect on tumor weights.Acknowledgments. These studies were supported by the Deutsche Forschungsgemeinschaft (DFG) within the SFB 90 Cardiovaskuläres System. Saralasin was a gift from Dr A.W. Castellion, Norwich Pharmacal Company, USA. We thank S. Thiele, P. Baumgärtl and D. Kurz for excellent technical assistance.