RESUMO
The present work was designed to evaluate the effects of functional suppression of complement regulatory proteins in vivo. Male Wistar rats were anesthetized with Nembutal and were intravenously injected with 1 mg/kg of F(ab')2 or Fab fraction of either monoclonal antibody 5I2, which inhibits the function of rat counterpart of mouse Crry/p65, or monoclonal antibody 6D1, which inhibits the rat counterpart of CD59. Mean arterial pressure was continuously measured for 30 min. When 5I2 was injected, there was a biphasic change of mean arterial pressure, namely, the rapid increase immediately after the injection (approximately 2 min, phase 1) and the subsequent fall and slow recovery (approximately 4-30 min, phase 2). These effects were completely abrogated by pretreatment of rats with cobra venom factor. Pretreatment with carboxypeptidase inhibitor, which inhibits inactivation of anaphylatoxins C3a and C5a, induced enhanced reduction of blood pressure. Circulating leukocytes and platelets were rapidly decreased 5 min after antibody injection and became normal by 2 h. Hematocrit and erythrocyte count were continuously increased up to 2 h after injection, suggesting that there was hemoconcentration due to increased vascular permeability. Immunofluorescence study revealed binding of antibody fragments and rat C3 along the capillaries of lung, heart, and liver 5 min after injection. In contrast to 5I2, F(ab')2 fraction of 6D1, though localized to the same areas and in similar amounts, had no significant effect on the parameters measured. These data suggest that the rat counterpart of mouse Crry/p65 plays a vital role in vivo by preventing the activation of autologous complement on vascular endothelium.
Assuntos
Anticorpos Monoclonais/imunologia , Antígenos CD/fisiologia , Ativação do Complemento , Glicoproteínas de Membrana/fisiologia , Receptores de Complemento/fisiologia , Animais , Antígenos de Superfície , Pressão Sanguínea , Antígenos CD59 , Permeabilidade Capilar , Complemento C3/metabolismo , Venenos Elapídicos/farmacologia , Leucócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ratos , Ratos Wistar , Receptores de Superfície Celular , Receptores de Complemento 3bRESUMO
The effects of GTP analogues and conditions in which various endogenous protein kinases were activated on photoaffinity labeling with [3H](+)PN200-110 (PN) of crude membranes from rat cardiac muscle and whole brain were investigated. Photoaffinity labeling with 20 nM [3H](+)PN of these crude membranes was decreased by 100 microM GTP-gamma-S, but not by 100 microM GTP or 100 microM GDP-beta-S. Similar results were obtained on the effects of GTP and its analogues on the specific binding of 20 nM [3H](+)PN to these crude membranes under the same conditions. Activation of endogenous protein kinases in these crude membranes did not influence the photoaffinity labeling with [3H](+)PN. These results suggested the binding sites, or DPH-sensitive, or L-type, calcium channels in curde membranes from rat cardiac muscle and whole brain are directly or indirectly modulated by endogenous GTP-binding protein, but not by various endogenous protein kinases in these crude membranes.
Assuntos
Encéfalo/metabolismo , Bloqueadores dos Canais de Cálcio/metabolismo , Di-Hidropiridinas , Guanosina Trifosfato/análogos & derivados , Miocárdio/metabolismo , Proteínas Quinases/metabolismo , Marcadores de Afinidade , Animais , Membrana Celular/metabolismo , Eletroforese em Gel de Poliacrilamida , Ativação Enzimática , Isradipino , Masculino , Fotoquímica , Ratos , Ratos Endogâmicos , TrítioRESUMO
We investigated whether the specific binding or labeling of 125I-omega-CgTX on crude membranes from chick whole brain was affected when endogenous GTP binding protein (G protein) was activated by GTP analogues, mastoparan (MP) and aluminum fluoride (AIF4-; AICl3 + NaF). Both GTPgammaS and Gpp(NH)p attenuated the inhibitory effect of selective N-type Ca channel inhibitors such as aminoglycoside antibiotics (AGs) or dynorphine (1-13)(Dyn) on specific 125I-omega-CgTX binding in a dose-dependent manner. On the other hand, the inhibitory effects of the divalent metal cations Cd2+, Co2+, Mg2+ and Mn2- on such binding were not attenuated by GTPgammaS. MP and AIF4- also attenuated the inhibitory effect of Neo on this binding similar to GTPgammaS. The attenuating effect of MP was enhanced by the presence of Mg2+ in a dose-dependent manner. However, GTP analogues, MP and AIF4-, did not affect binding or labeling without AGs or Dyn. GTPgammaS, MP and AIF4- also attenuated the specific labeling of a 215-kDa band in crude membranes with 125I-omega-CgTX using the cross-linker DSS (non-reduced condition) in the presence of Neo. These results indicate that there are direct or indirect relationships between N-type Ca channels and G proteins via binding sites for AGs or MP.
Assuntos
Compostos de Alumínio/farmacologia , Fluoretos/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Guanosina Trifosfato/análogos & derivados , Peptídeos/metabolismo , Venenos de Vespas/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Galinhas , Peptídeos e Proteínas de Sinalização Intercelular , Radioisótopos do Iodo , ômega-Conotoxina GVIARESUMO
Characteristics of specific 125I-omega-conotoxin GVIA (125I-omega-CgTX) binding and 125I-omega-CgTX labeling using bifunctional crosslinkers were systematically investigated in crude membranes from chick whole brain. Aminoglycosides and dynorphine A (1-13) inhibited the specific binding of 125I-omega-CgTX, but not that of the L-type calcium ion channel antagonist [3H](+)PN200-110. It seems likely that the inhibitory effect of dynorphine A (1-13) does not involve kappa-opiate receptors, based on results with the opiate receptor antagonist naloxone and the kappa-opiate receptor agonist U50488H. Spider venom, Cd2+ and La3+ inhibited the specific binding of 125I-omega-CgTX, as well as that of [3H](+)PN200-110. Various L-type Ca2+ channel antagonists did not affect the specific binding of 125I-omega-CgTX. 125I-omega-CgTX specifically labeled 135 kDa and 215 kDa bands in crude membranes under reduced and non-reduced conditions, respectively. The crosslinker disuccinimidyl suberate (DSS) yielded better 125I-omega-CgTX labeling than the other two crosslinkers tested. We investigated the effect of various Ca2+ channel antagonists on 125I-omega-CgTX labeling with DSS in detail, and found that there is a strong correlation between the effects of Ca2+ channel antagonists on 125I-omega-CgTX labeling of the 135 kDa band and specific 125I-omega-CgTX binding. These results suggest that aminoglycosides and dynorphine A (1-13) are specific inhibitors of specific 125I-omega-CgTX binding, and that labeling of the 135 kDa band with 125I-omega-CgTX using DSS involves the specific binding sites of 125I-omega-CgTX, perhaps including one of the neuronal N-type Ca2+ channel subunits in the crude membranes.
Assuntos
Canais de Cálcio/metabolismo , Venenos de Moluscos/metabolismo , Peptídeos/metabolismo , Marcadores de Afinidade , Animais , Encéfalo , Agonistas dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio/efeitos dos fármacos , Galinhas , Reagentes de Ligações Cruzadas/farmacologia , Técnicas In Vitro , Indicadores e Reagentes/farmacologia , Radioisótopos do Iodo , Isradipino/metabolismo , ômega-Conotoxina GVIARESUMO
We describe the development of acute renal failure and degenerative tubular lesions associated with local immune deposits in a patient with allogeneic bone marrow transplantation. A 21-year-old man with an acute myelocytic leukemia received a bone marrow graft from a cousin mismatched for a single HLA-DR locus antigen. Hemorrhagic cystitis due to adenovirus type 11 infection occurred 26 days after transplantation, and 17 days later the patients developed acute renal failure. A study of renal tissue obtained by needle biopsy showed degenerative and necrotic lesions, especially in the distal part of the nephron. By electron microscopy adenovirus type 11 particles were found in the nuclei of tubular cells and in cellular debris in tubular lumina. By immunofluorescence technique, granular immune deposits containing adenovirus type 11 related antigen(s), immunoglobulins, C3, and membrane attack complex (MAC) C5b-9 of the complement system were detected along the tubular basement membranes but not in glomeruli. The patient's IgG did not bind to normal human kidneys. These findings suggest that adenovirus type 11 directly induced acute tubular damage, and that the tubular immune deposits were formed "in situ" by viral antigens and circulating viral antibody.
Assuntos
Injúria Renal Aguda/etiologia , Adenovírus Humanos/imunologia , Anticorpos Antivirais/análise , Complexo Antígeno-Anticorpo/análise , Antígenos Virais/análise , Transplante de Medula Óssea , Túbulos Renais Distais/patologia , Adulto , Cistite/etiologia , Hemorragia/etiologia , Humanos , Túbulos Renais Distais/ultraestrutura , Leucemia Mieloide Aguda/cirurgia , Masculino , Microscopia Eletrônica , Necrose , Transplante HomólogoRESUMO
The characteristics of photoaffinity labeling with the calcium agonist [3H]Bay K 8644 (Bay) and the calcium antagonists [3H]nitrendipine (Nit) and (+)PN200-110 (PN) of crude membranes from rat skeletal, cardiac, ileal, and uterine muscles and whole brain were investigated. In all these crude membranes, [3H](+)PN (20 nM) was mainly photoincorporated into one protein band with a molecular weight of 30,000 - 41,000 Da. It was also incorporated into some other bands of all these crude membranes. The photoincorporation of [3H](+)PN into these crude membranes was inhibited by the presence of 20 microM unlabeled (+)PN. The photoincorporation of [3H](+)PN into these crude membranes depended on its dose and on the time of UV irradiation. No incorporation of [3H](+)PN was observed in the absence of UV irradiation. The incorporation was not affected by the presence of 1 mM CaCl2 and/or 0.15 M NaCl, but was significantly decreased by 20 microM (+)PN and slightly decreased by 20 microM (-)PN, 20 microM Bay, 1 mM diltiazem, or 1 mM verapamil. Namely, enantiomers of PN caused various extents of stereoselective inhibition of photoaffinity labeling by [3H](+)PN of specific protein bands in these crude membranes. [3H]Nit was photoincorporated into these crude membranes in the same way as [3H](+)PN, but [3H]Bay was not photoincorporated. However, 20 microM unlabeled Nit did not consistently inhibit photoaffinity labeling with [3H]Nit. These findings suggested that measurement of photoaffinity of crude membranes from rat skeletal, cardiac, and uterine muscles and whole brain with [3H](+)PN by UV irradiation is a useful method for investigating the characteristics of the voltage-dependent calcium channels that are affected by 1,4-dihydropyridine derivatives.
Assuntos
Encéfalo/metabolismo , Di-Hidropiridinas/metabolismo , Músculos/metabolismo , Éster Metílico do Ácido 3-Piridinacarboxílico, 1,4-Di-Hidro-2,6-Dimetil-5-Nitro-4-(2-(Trifluormetil)fenil)/metabolismo , Marcadores de Afinidade , Animais , Autorradiografia , Eletroforese em Gel de Poliacrilamida , Feminino , Íleo/metabolismo , Técnicas In Vitro , Masculino , Membranas/metabolismo , Músculo Liso/metabolismo , Miocárdio/metabolismo , Nitrendipino/metabolismo , Ratos , Espectrometria de Fluorescência , Útero/metabolismoRESUMO
The characteristics of the specific bindings of [3H]nitrendipine (Nit) and [3H](+)PN200-110 (PN) to crude membranes from rat skeletal, cardiac, and uterine muscle and whole brain were investigated, with special interest in the effect of UV irradiation on these bindings. The specific bindings of [3H]Nit and [3H](+)PN to these crude membranes were saturable and reversible. The specific bindings of [3H]Nit to all these membranes except crude skeletal membranes was maximum in the presence of 0.15 M NaCl plus 1 mM CaCl2 and minimal in the absence of these ions, but the specific bindings of [3H](+)PN to these crude membranes was not affected significantly by these ions. A calcium agonist and antagonists inhibited the specific bindings of [3H]Nit and [3H](+)PN to these crude membranes, the order of their inhibitory effects on specific [3H]Nit bindings being roughly Nit greater than or equal to (+)PN greater than or equal to (-)PN much greater than Bay K 8644 (Bay) greater than verapamil (Ver) greater than diltiazem (Dil). In crude skeletal membranes only, PN caused significant stereospecific inhibition. The order of inhibitions of specific [3H](+)PN bindings to these crude membranes was generally (+)PN greater than Nit greater than or equal to (-)PN greater than Bay much greater than Ver greater than or equal to Dil. In all these crude membranes, UV irradiation completely prevented decrease in the amount of specific binding of [3H](+)PN binding on addition of excess unlabeled (+)PN. These findings suggested that [3H]Nit and [3H](+)PN bind to voltage-sensitive calcium channels in crude membranes from rat skeletal, cardiac, and uterine muscle and whole brain, and that UV irradiation changes the specific bindings of [3H]Nit and [3H](+)PN from reversible to irreversible bindings.
Assuntos
Bloqueadores dos Canais de Cálcio/metabolismo , Nitrendipino/metabolismo , Oxidiazóis/metabolismo , Animais , Feminino , Técnicas In Vitro , Isradipino , Masculino , Membranas/metabolismo , Membranas/efeitos da radiação , Músculo Liso/metabolismo , Músculos/metabolismo , Ratos , Ratos Endogâmicos , Espectrofotometria Ultravioleta , Fatores de Tempo , Raios UltravioletaRESUMO
The effects of dibutyrl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by the P2 fraction of Gray and Whittaker were investigated with the following results. (1) db-cGMP inhibited the initial rate of potassium-stimulated 45Ca-uptake in a dose-dependent manner in 0.1 mM Ca0 medium, but had no effect on the uptake in low K+ medium. In 0.1 mM Ca0 medium, the concentration of db-cGMP causing 50% inhibition was about 3 mM. db-cAMP (5 mM) had no effect on the uptake. (2) db-cGMP-inhibited potassium-stimulated 45Ca uptake in 1 mM Ca0 medium, though less than in 0.1 mM Ca0 medium. (3) db-cGMP inhibited potassium-stimulated 45Ca uptake by synaptosomes (pinched-off nerve terminals) more than the uptakes by other subfractions of P2 fraction. It is suggested from the results that cGMP inhibits the Ca influx resulting from depolarization of the nerve endings in situ.
Assuntos
Encéfalo/efeitos dos fármacos , Cálcio/metabolismo , GMP Cíclico/análogos & derivados , Dibutiril GMP Cíclico/farmacologia , Potássio/metabolismo , Sinaptossomos/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Bucladesina/farmacologia , Humanos , Masculino , Ratos , Sinaptossomos/metabolismoRESUMO
The effects of dibutyryl cyclic GMP (db-cGMP) and dibutyryl cyclic AMP (db-cAMP) on potassium-stimulated 45Ca uptake by cortical slices of rat brain were investigated. db-cGMP specifically inhibited the initial rate of potassium-stimulated 45Ca uptake in a dose-dependent manner. Our findings supported the suggestion that cyclic GMP may play a regulatory role in depolarization-elicited Ca2+ influx in nerve endings in situ.
Assuntos
Bucladesina/farmacologia , Cálcio/metabolismo , Córtex Cerebral/metabolismo , GMP Cíclico/análogos & derivados , Dibutiril GMP Cíclico/farmacologia , Potássio/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Córtex Cerebral/efeitos dos fármacos , Técnicas In Vitro , Cinética , Masculino , RatosRESUMO
The effects of neurotransmitter candidates and the characteristics of the stimulatory effect of L-glutamic acid (L-Glu) on 45Ca uptake by rat brain slices were investigated. 45Ca uptake was significantly stimulated by acetylcholine, serotonin and especially L-Glu, but not by other neurotransmitter candidates. L-Glu caused dose-dependent stimulation of 45Ca uptake (L-Glu-stimulated 45Ca uptake), its effect being half-maximal at 1 microM. The related compounds D-glutamic acid, D,L-alpha-aminoadipic acid and N-methyl-D,L-glutamic acid (final conc. of 10 microM) also stimulated 45Ca uptake, but less than 10 microM L-Glu. D,L-alpha-Methylglutamic acid and L-glutamic acid diethylether (final conc. of 10 microM), which are specific inhibitors of L-Glu, inhibited L-Glu-stimulated 45Ca uptake. Mg,Ca-ATPase activity was hardly affected by a concentration of 10 microM L-Glu that caused maximal stimulation of 45Ca uptake. These findings suggest that L-Glu-stimulated 45Ca uptake by brain cortical slices is linked to L-Glu receptor.
Assuntos
Cálcio/metabolismo , Córtex Cerebral/metabolismo , Glutamatos/farmacologia , Neurotransmissores/farmacologia , Acetilcolina/farmacologia , Animais , Dopamina/farmacologia , Ácido Glutâmico , Histamina/farmacologia , Técnicas In Vitro , Masculino , Norepinefrina/farmacologia , Ratos , Ratos Endogâmicos , Serotonina/farmacologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
The inhibitory effects of ketanserin and spiroperidol (a neuroleptic drug) on the contractile response of isolated rat uterus to serotonin (5-HT) were investigated. Ketanserin caused non-competitive inhibition of the contractile response to 5-HT and showed more selective inhibition than the other 5-HT antagonists tested. The inhibitory effect of spiroperidol was comparable with the effects of classical 5-HT antagonists. These results suggest that ketanserin and spiroperidol selectively inhibit the contractile response of isolated rat uterus to 5-HT.
Assuntos
Butirofenonas/farmacologia , Piperidinas/farmacologia , Antagonistas da Serotonina/farmacologia , Espiperona/farmacologia , Contração Uterina/efeitos dos fármacos , Animais , Estradiol/farmacologia , Feminino , Ketanserina , Ovário/fisiologia , Ratos , Ratos EndogâmicosRESUMO
[3H]Ketanserin, a specific serotonin (5-HT) antagonist, was used to investigate whether 5-HT receptors increased in the uterine membranes of ovariectomized rats on administration of 17 beta-estradiol-3-benzoate (estradiol) and also to investigate the characteristics of specific [3H]ketanserin binding to the uterine membranes from estradiol-treated ovariectomized rat. Administration of estradiol significantly increased the amount of [3H]ketanserin specifically bound at equilibrium but did not change the apparent affinity of specific [3H]ketanserin binding. The specific [3H]ketanserin binding to estradiol-treated ovariectomized preparations was rapid and reversible. The Scatchard plots of the saturation curves of specific [3H]ketanserin binding to untreated and estradiol-treated ovariectomized preparations were convex. The apparent Ki values of various serotonergic agents deduced from displacements by these compounds of specific [3H]ketanserin binding to estradiol-treated ovariectomized preparations were two to four orders of magnitude smaller than those of adrenergic, dopaminergic and histaminergic agents. These results suggest that [3H]ketanserin binds mainly to 5-HT receptors in the uterine membranes of estradiol-treated ovariectomized rats.
Assuntos
Estradiol/farmacologia , Piperidinas/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/metabolismo , Útero/metabolismo , Animais , Sítios de Ligação , Castração , Feminino , Técnicas In Vitro , Ketanserina , Membranas/metabolismo , Ratos , Ratos Endogâmicos , TrítioRESUMO
Rat uterine smooth muscle was preincubated in Ca-depleted modified Locke-Ringer solution to investigate the correlation between the 32Pi incorporation into phosphatidic acid induced by acetylcholine and the contractile response to acetylcholine induced by the addition of CaCl2 (Ca influx). The results showed that in rat uterine smooth muscle under these conditions phosphatidic acid does not act as a Ca ionophore or as a trigger for opening the Ca channel.
Assuntos
Acetilcolina/farmacologia , Cálcio/metabolismo , Ácidos Fosfatídicos/metabolismo , Útero/metabolismo , Animais , Feminino , Técnicas In Vitro , Radioisótopos de Fósforo , Ratos , Contração Uterina/efeitos dos fármacosRESUMO
An acidic toxic extract from the sea urchin T. pileolus inhibited time-dependent 45Ca2+ uptake in chick P2 fraction (IC50 about 10 ng/ml). This toxic extract is susceptible to trypsin. The inhibitory effect probably relate to Na+/Ca2+ exchanger.
Assuntos
Química Encefálica/efeitos dos fármacos , Cálcio/metabolismo , Galinhas/metabolismo , Toxinas Marinhas/farmacologia , Ouriços-do-Mar/química , Extratos de Tecidos/farmacologia , Animais , Radioisótopos de Cálcio , Cromatografia por Troca Iônica , Hidrólise , Técnicas In Vitro , Cinética , Toxinas Marinhas/química , Desnaturação Proteica , Extratos de Tecidos/química , TripsinaRESUMO
To clarify the mechanism by which the toxic abstract from Toxopneustes pileolus inhibits time-dependent (Time-dep.) Ca(2+) uptake in crude synaptosome fraction, the effective component from pedicellarial venom of the sea urchin was purified. The crude extracts were purified by a series of steps including ion exchange (DEAE-sephadex-A25 gel), gel filtration (with Superdex-2000 and Superdex-peptide columns) and reversed-phase chromatography (Sephasil-C18 column). The effective component that inhibited Time-dep. 45Ca(2+) uptake was purified and named UT841. Its IC(50) was determined to be lower than 35ng/ml. UT841 is an acidic protein with an apparent molecular weight of about 18,000. The N-terminal sequence (40 amino acids) was almost identical to that of Contractin A (a protein purified from the same kind of venom which induces smooth muscle contraction). Even though it is unclear whether or not UT841 is Contractin A, Ca(2+) mobilization in nerve cells was shown to be influenced by UT841. This investigation also revealed that a donor of nitric oxide, arachidonic acid and an inhibitor of phospholipase C selectively inhibit Time-dep. (45)Ca(2+) uptake. These results suggest that UT841 purified from sea urchin venom may affect Time-dep. (45)Ca(2+) uptake through the metabolism of some lipids and nitric oxide.
Assuntos
Encéfalo/efeitos dos fármacos , Cálcio/metabolismo , Ouriços-do-Mar/patogenicidade , Sinaptossomos/efeitos dos fármacos , Peçonhas/toxicidade , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Galinhas , Dados de Sequência Molecular , Sinaptossomos/metabolismo , Fatores de Tempo , Peçonhas/químicaRESUMO
We describe a 66-year-old man who developed renal failure related to granulomatous renal sarcoidosis without systemic manifestations. Renal failure was severe enough to require hemodialysis transiently. Renal biopsy of this patient revealed the central necrosis of the granuloma which is usually absent in sarcoid granuloma. Serum level of angiotensin converting enzyme (ACE) was not helpful for diagnosis in this patient because serum ACE level is often elevated in the condition of chronic renal failure. Immunohistochemical detection of ACE was of diagnostic value in this patient. Subsequent course in which glucocorticoid was used for therapy was consistent with the diagnosis. This is the first report of identification of ACE in renal sarcoid granuloma.
Assuntos
Nefropatias/diagnóstico , Rim/patologia , Peptidil Dipeptidase A/análise , Sarcoidose/diagnóstico , Idoso , Biópsia , Imunofluorescência , Humanos , Rim/enzimologia , Nefropatias/complicações , Nefropatias/enzimologia , Masculino , Microscopia Eletrônica , Microscopia de Fluorescência , Necrose , Insuficiência Renal/etiologia , Sarcoidose/complicações , Sarcoidose/enzimologiaRESUMO
The aim of this study was to observe whether a low dosage of zinc induced mouse pancreatic injury. Dosages of zinc from 0.1 to 50 mg/kg were injected subcutaneously in mice, and plasma and pancreatic clinical parameters were observed 3-24 h after the injection. Plasma alpha-amylase activity increased 10 and 24 h after the injection of 25 or 50 mg/kg of zinc, whereas pancreatic alpha-amylase activity decreased 3 h after more than 5 mg/kg of zinc was injected. The activity recovered after 24 h except in the group injected with 50 mg/kg of zinc. The plasma glucose level did not change when less than 25 mg/kg of zinc was injected. The pancreatic zinc contents increased 3 h after more than 1 mg/kg of zinc was injected. The pancreatic metallothionein (MT) contents increased 6 h after the injection of 1 mg/kg of zinc. In addition, when more than 5 mg/kg of zinc was injected, the MT content increased at 3 h. In histochemical observations, cell damages such as fibrosis and necrosis were observed in pancreatic exocrine cells, but not in cells of Langerhans islets. From the present study, a single injection of a low dosage of zinc induces injury in pancreatic exocrine cells, but not endocrine cells.