RESUMO
INTRODUCTION: The ALPSS procedure has been recently introduced as an alternative to PVE for liver volume augmentation in cases of planned right trisectionectomy with small future RLV and high risk of PHLF. We retrospectively analysed our single centre experience with 15 ALPPS procedures in order to better assess the limits and indications of the procedure. PATIENTS AND METHODS: The following volumetric parameters were evaluated: total liver volume (TLV), remnant liver volume (RLV), remnant liver volume to total liver volume ratio (RLV/TLV), remnant liver volume to body weight ratio (RLV/BWR) and median volume gain. The ALPPS procedure was usually considered when RLV/TLV <â25â% or RLV/BWR <â0.5. The ALPPS procedure consisted of phase 1 (in situ splitting of the liver), interphase (waiting for liver regeneration) and phase 2 (completion of right trisectionectomy). Postoperative complications were reported according to the Dindo-Clavien classification. Patient survival, late complications and tumour recurrence were analysed. RESULTS: Between November 2010 and September 2013, we performed 15 ALPPS procedures in 10 patients with primary liver tumours (5 h-CCA, 4 i-CCA and 1 HCC) and in 5 with CRLM. The preoperative RLV/TLV ratio was 22.6â% (15.7â-â29.2) and the RLV/BWR 0.46 (0.22â-â0.66). After 10 days (range 8â-â16) the RLV/TLV ratio and RLV/BWR increased up to 36.3â% (30â-â59.2â%) and 0.67 (0.5â-â1.2) respectively, with a median volume gain of 87.2â% (23.8â-â161â%). The time interval between phases 1 and 2 was 13 days (9â-â18). An R0 status was reached in 13 patients and R1 in 2. The overall postoperative morbidity was 66.7â%. After phase 1, 8 patients experienced 19 complications and 7 none. After phase 2, 11 patients experienced 36 complications and 4 none. Four patients died postoperatively after 22 days (9â-â36 days) resulting in a postoperative mortality of 28.7â%. After a median follow-up of 17 months (1â-â33), 10 out of 15 patients are still alive (survival rate 66.6â%). Four patients (2 i-CCA, 1 CRLM, 1 HCC) developed tumour recurrences (2 intrahepatic and 2 extrahepatic). One patient with i-CCA died at POM 4 secondary to peritoneal carcinosis. DISCUSSION: The actual high morbidity and mortality rates related to the ALPPS procedure should lead us to a more cautious selection of the candidates for this operation and restriction of the indications through an accurate work-up based on interdisciplinary cooperation among hepatologists, oncologists, radiologists and surgeons.
Assuntos
Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Veia Porta/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Ligadura/métodos , Neoplasias Hepáticas/patologia , Masculino , Tamanho do Órgão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
The size of the primary tumour is considered the most important risk factor for the development of metastasis or local recurrence in case of gastrointestinal stromal tumour (GIST). Until now no prospective data are available in the literature about the role of neadjuvant therapy with Imatinib. Between 2009 and 2012 seven patients with a giant GIST >â20âcm underwent a neadjuvant treatment with Imatinib, a radical operation, followed by an adjuvant therapy. These patients were controlled with regard to peri- and postoperative morbidity and disease-free survival. Two patients were considered not resectable and one patient showed liver metastasis at the time of diagnosis. RECIST responses to the neoadjuvant Imatinib were: 2/7 patients with stable disease, 3/7 partial response, 2/7 partial response with down-staging (resectable disease). Because of the following tumour localisations (6 gastric and 1 rectal), six gastrectomies (one en-bloc with left pancreas) and one Holm operation were performed. The patient with simultaneous liver metastasis developed a tumour progression during the follow-up but the others are still tumour free after 2 years. We detected a significant tumour volume regression due to the neadjuvant chemotherapy in cases of GIST >â20âcm (30â%). Our series showed good results for a neadjuvant therapy in cases of giant GIST with the achievement of 100â% R0 resection without a high morbidity rate (in the literature a tumor size >â10âcm and poor localisation is associated to a high risk of R1â-â2 and high morbidity). Peri- and postoperative morbidity are acceptable and the tumour free survival at 2 years is 85â%.
Assuntos
Benzamidas/administração & dosagem , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Idoso , Antineoplásicos/administração & dosagem , Feminino , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Projetos Piloto , Resultado do Tratamento , Carga TumoralAssuntos
Recidiva Local de Neoplasia/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Próteses e Implantes , Sarcoma/cirurgia , Neoplasias Torácicas/cirurgia , Adolescente , Adulto , Diafragma/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonectomia/efeitos adversos , Desenho de Prótese , Procedimentos de Cirurgia Plástica/efeitos adversos , Costelas/cirurgia , Escoliose/etiologia , Parede Torácica/cirurgia , Resultado do TratamentoRESUMO
The Department of Thoracic Surgery of the National Institute of Cancer in Milan developed a new rib-cage prosthesis which tries to combine flexibility, protection and bio-compatibility. This new replacement concept has been implanted in many patients, showing cheering results in term of reconstructions simplicity, postoperative complications reduction and patients comfort. This paper investigates and discusses in detail the mechanical behavior of the innovative rib cage prosthesis. Mechanical strength and stiffness are numerically evaluated in order to asses its limits and if it is fully compatible with patients 'normal' life.
Assuntos
Próteses e Implantes , Costelas/fisiologia , Parede Torácica/fisiologia , Fenômenos Biomecânicos , Humanos , Modelos Biológicos , Implantação de Prótese , Estresse MecânicoRESUMO
BACKGROUND: Paratesticular liposarcomas are almost always mistakenly diagnosed as inguinal hernias subsequently followed by inadequate operation. METHODS: 14 consecutive patients with paratesticular liposarcoma were retrospectively reviewed. Preoperative management was evaluated. Disease-free and overall survival were determined. RESULTS: In 11 patients primary and in 3 patients recurrent liposarcoma of the spermatic cord were diagnosed. Regarding primary treatment in primary surgical intervention resection was radical (R0) in 7 of 14 (50%) patients, marginal (R1) in 6 (43%) patients, and incomplete with macroscopic residual tumour (R2) in 1 (7%) patient. Primary treatment secondary surgical intervention was performed in 4 patients: resection was radical (R0) in 3 (75%) patients and marginal (R1) in 1 (25%) patient. Regarding secondary treatment in recurrent disease resection was marginal (R1) in 3 patients (100%). Final histologic margins were negative in 10 patients with primary disease (71%) and positive in 4 patients with subsequent recurrent disease. After radical resection disease-free survival rates at 3 years were 100%. Overall survival at 4.5 years (54 (18-180) months) was 64%. CONCLUSION: An incomplete first surgical step increases the number of positive margins leading to local recurrences and adverse prognoses. Aggressive surgery should be attempted to attain 3-dimensional negative margins.
Assuntos
Neoplasias dos Genitais Masculinos/cirurgia , Lipossarcoma/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasia Residual/cirurgia , Cordão Espermático/cirurgia , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Neoplasias dos Genitais Masculinos/diagnóstico , Neoplasias dos Genitais Masculinos/mortalidade , Humanos , Lipossarcoma/diagnóstico , Lipossarcoma/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual/diagnóstico , Neoplasia Residual/mortalidade , Orquiectomia/métodos , Prognóstico , Estudos Retrospectivos , Cordão Espermático/patologia , Taxa de SobrevidaRESUMO
In normal striata, pre-treatment with the D-1 antagonist SCH 23390 (250 and 25 micrograms kg-1, s.c.) completely and lastingly prevented the D-2 antagonist remoxipride (REM) from increasing acetylcholine (ACh) release; post-treatment did not affect REM action. In alpha-methyl-p-tyrosine (alpha-MpT) dopamine (DA)-depleted striata, however, pretreatment with SCH 23390 resulted in a transient impairment of REM induced stimulation of ACh release but post-treatment still had no effect. Two different mechanisms therefore seem to be involved in D-2 antagonist-induced stimulation of ACh release; the antagonists indirectly activate a D-1 receptor-mediated facilitatory mechanism regulating cholinergic function, and directly block a D-2 receptor-mediated inhibitory one. In normal rats, in an early phase after D-2 antagonist administration, only the first mechanism is operative; in a later phase, both mechanisms cooperate in the stimulation of ACh release. When DA release is impaired by alpha-MpT, the D-2 inhibitory receptor mechanism becomes more important than the D-1 facilitatory one in controlling ACh release.
Assuntos
Acetilcolina/metabolismo , Antipsicóticos/farmacologia , Corpo Estriado/metabolismo , Receptores de Dopamina D1/efeitos dos fármacos , Receptores de Dopamina D2/efeitos dos fármacos , Animais , Benzazepinas/farmacologia , Corpo Estriado/efeitos dos fármacos , Diálise , Dopamina/metabolismo , Feminino , Metiltirosinas/farmacologia , Microdiálise , Ratos , Remoxiprida/farmacologia , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , alfa-MetiltirosinaRESUMO
Galanin (GAL) administered intracerebroventricularly (i.c.v.) induced a strong and long-lasting increase in the basal acetylcholine (ACh) release from striata of freely moving rats only when the excitatory corticostriatal input was removed, while its effect was transient in striata of sham-operated rats. This effect was dose-dependent (0.78, 1.56 and 3.12 nmol) and was completely prevented by the GAL receptor antagonist, galantide. GAL injected locally (3.12 nmol) in deafferented striata also induced a persistent increase in ACh release although to a lower extent. The impairment of monoaminergic neurotransmission caused by alpha-methylparatyrosine or p-chlorophenylalanine, respectively inhibitors of catecholamine and serotonin synthesis, completely prevented the rise in ACh output from deafferented striata while the muscarinic antagonist, scopolamine (0.5 mg/kg, s.c.), failed to do it. The data suggest that GAL in the deafferented striatum facilitates basal ACh release through an indirect mechanism. The effect seems to be at least partly mediated by an action of GAL on specific receptors in the striata.
Assuntos
Acetilcolina/metabolismo , Corpo Estriado/metabolismo , Movimento/fisiologia , Neuropeptídeos/fisiologia , Peptídeos/fisiologia , Animais , Diálise , Lobo Frontal/fisiologia , Galanina , Masculino , RatosRESUMO
Using synthetic N-terminal fragments of galanin, galanin (1-7), galanin (1-9), galanin (1-12) and galanin (1-16), we have shown that the minimal sequence required for inhibition of acetylcholine release in vivo from rat ventral hippocampus corresponds to galanin (1-12). The fragment (1-9) displays activity in vivo but only at a very high concentration of 6.23 nmol while galanin (1-7) and C-terminal fragment (17-29) are without effect. Binding studies showed that galanin (1-16) and galanin (1-12) bind with submicromolar IC50 values to rat hippocampal galanin receptors. Galanin (1-9) has substantially lower affinity towards rat ventral hippocampal galanin receptor.
Assuntos
Acetilcolina/metabolismo , Hipocampo/metabolismo , Neuropeptídeos/farmacologia , Fragmentos de Peptídeos/farmacologia , Peptídeos/farmacologia , Animais , Ligação Competitiva/efeitos dos fármacos , Galanina , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Ligantes , Masculino , Membranas/efeitos dos fármacos , Membranas/metabolismo , Ratos , Ratos Endogâmicos , Ratos Sprague-Dawley , Receptores de Galanina , Receptores dos Hormônios Gastrointestinais/efeitos dos fármacos , Receptores dos Hormônios Gastrointestinais/metabolismo , Escopolamina/antagonistas & inibidores , Escopolamina/farmacologia , Relação Estrutura-AtividadeRESUMO
The effects of intracerebroventricular (i.c.v.) injections of pertussis toxin were investigated on the inhibitory action of galanin on acetylcholine release and phosphoinositide breakdown stimulated by muscarinic agents in rat ventral hippocampus. Pertussis toxin (0.6 micrograms, i.c.v., 96 h) counteracted the in vitro inhibitory effect of galanin (3.1 nmol) on phosphoinositide breakdown stimulated by carbachol without altering the stimulatory action of the cholinergic agonist on signal transduction, in miniprisms from rat ventral hippocampus. Pertussis toxin also abolished the in vivo effect of galanin on scopolamine-stimulated acetylcholine release in vivo but did not affect basal acetylcholine release. The results indicate that pertussis toxin-sensitive G-protein(s) mediates the galanin receptor regulation of pre- and postsynaptic cholinergic functions in the ventral hippocampus.
Assuntos
Acetilcolina/metabolismo , Carbacol/farmacologia , Ventrículos Cerebrais/fisiopatologia , Proteínas de Ligação ao GTP/fisiologia , Hipocampo/fisiologia , Peptídeos/farmacologia , Toxina Pertussis , Fosfatidilinositóis/metabolismo , Escopolamina/farmacologia , Fatores de Virulência de Bordetella/farmacologia , Animais , Membrana Celular/efeitos dos fármacos , Membrana Celular/fisiologia , Ventrículos Cerebrais/efeitos dos fármacos , Proteínas de Ligação ao GTP/efeitos dos fármacos , Galanina , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Injeções Intraventriculares , Masculino , Neuropeptídeos/farmacologia , Ratos , Ratos Endogâmicos , Valores de Referência , Escopolamina/antagonistas & inibidores , Fatores de Virulência de Bordetella/administração & dosagemRESUMO
The effect of tianeptine on in vivo acetylcholine (ACh) release from brain hemispheric regions of freely moving rats was investigated using the microdialysis technique coupled with a sensitive radioenzymatic method. Tianeptine, at the dose of 30 mg/kg i.p., reduced ACh release from dorsal hippocampi by 40% in 40 min, and induced a 30% decrease of ACh output from frontal cortices while at the doses of 10 and 20 mg/kg it had no effect. In striata the drug did not significantly affect ACh release although it showed a tendency to increase it. The ACh content in the three areas considered was not affected by tianeptine at above doses. The drug did not alter choline-o-acetyltransferase and acetylcholinesterase activities suggesting that it did not influence the cholinergic system through direct action on the ACh metabolism; furthermore, it did not influence the sodium-dependent high-affinity uptake of choline in striatum, cortex and hippocampus. Impairment of serotonergic (5-HT) neurotransmission by chemical lesion of the median raphe nucleus or by metergoline, a blocker of 5-HT receptors, antagonized the cholinergic effect of tianeptine. The involvement of the serotonergic system is specific because lesions of the noradrenergic dorsal bundle failed to prevent the inhibitory action of tianeptine. The present data suggest that 5-HT may mediate the effect of tianeptine on the cholinergic system in dorsal hippocampi.
Assuntos
Antidepressivos Tricíclicos/farmacologia , Encéfalo/efeitos dos fármacos , Fibras Colinérgicas/efeitos dos fármacos , Serotonina/farmacologia , Tiazepinas/farmacologia , Acetilcolina/metabolismo , Acetilcolinesterase/metabolismo , Animais , Encéfalo/metabolismo , Encefalopatias/fisiopatologia , Colina/metabolismo , Colina O-Acetiltransferase/metabolismo , Fibras Colinérgicas/metabolismo , Clomipramina/farmacologia , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Relação Dose-Resposta a Droga , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Núcleos da Rafe/fisiologia , Ratos , Ratos Endogâmicos , Sódio/fisiologiaAssuntos
Acetilcolina/metabolismo , Corpo Estriado/metabolismo , Receptores Dopaminérgicos/fisiologia , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Benzazepinas/farmacologia , Cromanos/farmacologia , Dextroanfetamina/farmacologia , Dopaminérgicos/farmacologia , Antagonistas de Dopamina , Feminino , Microdiálise , Pargilina/farmacologia , Ratos , Receptores Dopaminérgicos/classificação , Receptores Dopaminérgicos/efeitos dos fármacos , Taxa SecretóriaAssuntos
Arteriopatias Oclusivas , Doença Aguda , Aneurisma/diagnóstico , Aneurisma/diagnóstico por imagem , Angiografia , Arteriopatias Oclusivas/diagnóstico , Arteriopatias Oclusivas/diagnóstico por imagem , Diagnóstico Diferencial , Humanos , Perna (Membro)/irrigação sanguínea , Trombose/diagnóstico , Trombose/diagnóstico por imagemRESUMO
BACKGROUND: The aim of this study was to prove the existence of a direct relationship between the comprehensive strategy of trauma management and an enhancement in outcome. Tests were carried out on the impact of the Niguarda Trauma Team System on mortality rates due to severe trauma. METHODS: The epidemiological data was retrospectively reviewed along with, the severity scores: Abbreviated Injury Scale (AIS), Injury Severity Score (ISS), Revised Trauma Score (RTS), Probability of survival (Ps) and the outcome of severe trauma admitted to Niguarda hospital between October 2002 and September 2005. All data were collected from the Trauma Registry of the Niguarda Hospital. Two subsequent periods of 20 and 16 months were compared. RESULTS: Nine hundred forty-two severe traumas (94.05% blunt trauma) were recorded with an overtriage rate of 36.09%. Most patients were admitted for bone and muscular injuries (52.22%). Excluding the patients who were overtriaged, there were 129 patients who died. Comparing the two periods, the Authors observed a significant reduction in mortality from 22.56% to 19.75%, mainly related to a decrease in early mortality due to hemodynamic instability. Central nervous system injury was the main cause of death (65%). Average hospital stay significantly decreased from 17.01+/-12.07 days to 14.97+/-10.34 days. CONCLUSION: Introducing a comprehensive strategy of severe trauma management, the Niguarda Trauma Team System had a significant impact on mortality rates and hospital stay.
Assuntos
Ferimentos e Lesões/mortalidade , Ferimentos e Lesões/terapia , Adulto , Feminino , Humanos , Escala de Gravidade do Ferimento , Masculino , Equipe de Assistência ao Paciente , Estudos Retrospectivos , Fatores de TempoRESUMO
Intrastriatal application of the D1 antagonist SCH 23390 by two procedures, reverse dialysis (20 microM) and local injection (0.45 nmol per striatum), elicited a reduction in acetylcholine (ACh) release superimposable on that induced by systemic administration. The novel selective D1 antagonist SCH 39166 produced a similar decreasing effect on striatal ACh release on local injection (0.45 nmol per striatum). On the other hand, local application of SCH 23390 into the frontal cortices (0.45 nmol per side) failed to alter striatal ACh overflow, indicating that the drug does not diffuse out of its injection site to any significant extent. The dopamine release inducer d-amphetamine (2 mg/kg s.c.) and the dopamine uptake inhibitor cocaine raised ACh release like the D1 agonists. These effects were completely blocked by 10 microM SCH 23390 applied by reverse dialysis. The results suggest that D1 receptors regulating ACh release are located in the striatum.
Assuntos
Acetilcolina/metabolismo , Corpo Estriado/metabolismo , Dopamina/fisiologia , Receptores de Dopamina D1/fisiologia , Acetilcolina/antagonistas & inibidores , Animais , Benzazepinas/farmacologia , Cocaína/farmacologia , Dextroanfetamina/farmacologia , Feminino , Ratos , Ratos Endogâmicos , Receptores de Dopamina D1/metabolismoRESUMO
The tumor-promoting activity of two beta-adrenoreceptor blocking agents, propranolol and atenolol, was tested in a two-stage protocol of hepatocarcinogenesis in male and female Fischer 344 rats. Propranolol is a lipophilic non-selective beta-blocker mainly eliminated via the liver; atenolol is a hydrophilic beta 1-selective blocking agent, mainly eliminated via the kidney. Animals were initiated with a single dose of diethylnitrosamine (DEN, 200 mg/kg, i.p.) and, after 17 days of recovery, were continuously treated with propranolol (75-100 mg/kg) or atenolol (300 mg/kg) by gavage for up to 21 months. Rats given phenobarbital (0.05% in the diet) were used as positive controls. After 2, 4 and 8 months of promotion, preneoplastic lesions were quantified by staining sections of liver for gamma-glutamyltranspeptidase (GGT). In non-initiated rats, neither propranolol nor atenolol influenced the development of spontaneous preneoplastic or neoplastic liver lesions. The results obtained in DEN-initiated rats given propranolol cannot be unequivocally interpreted. In the male, propranolol seemed to be ineffective. In the female, there was weak enhancement of DEN-induced GGT foci at 4 and 8 months and of neoplastic lesions thereafter. However, there was great interindividual variability in focus and tumor yields. Unfortunately, due to the high incidence of liver tumors in rats given DEN alone and the small number of propranolol-treated rats that survived until the end of the experiment, no definite conclusion can be drawn about the modifying potential of this beta-blocker on liver carcinogenesis. There was no evidence of liver tumor promotion in DEN-initiated rats of either sex given atenolol.
Assuntos
Atenolol/toxicidade , Carcinógenos/toxicidade , Neoplasias Hepáticas Experimentais/induzido quimicamente , Propranolol/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Dietilnitrosamina , Feminino , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas Experimentais/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/patologia , Ratos , Ratos Endogâmicos F344 , Fatores Sexuais , gama-Glutamiltransferase/análiseRESUMO
The 20-amino acid peptide M-15 binds with high affinity (IC50 approximately 0.1 nM) to 125I-labeled galanin (125I-GAL) binding sites in membranes from the ventral hippocampus, midbrain, and rat spinal cord. Receptor autoradiographic studies show that M-15 can displace 125I-GAL from all labeled sites. M-15 acts as a reversible high-affinity antagonist in blocking the inhibitory effects of GAL on the evoked release of acetylcholine in vivo in the hippocampus and on the GAL-induced hyperpolarization of locus coeruleus neurons in slices. M-15 also blocks the facilitatory effects of GAL on the spinal flexor reflex. Thus, the chimeric peptide M-15 [GAL-(1-13)-substance P-(5-11)amide] represents the first antagonist to the neuronal actions of GAL.
Assuntos
Hipocampo/fisiologia , Locus Cerúleo/fisiologia , Neurônios/fisiologia , Neuropeptídeos/farmacologia , Peptídeos/farmacologia , Receptores dos Hormônios Gastrointestinais/fisiologia , Medula Espinal/fisiologia , Substância P/análogos & derivados , Acetilcolina/farmacologia , Animais , Autorradiografia , Sítios de Ligação , Ligação Competitiva , Membrana Celular/metabolismo , Quimera , Condutividade Elétrica/efeitos dos fármacos , Galanina , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Radioisótopos do Iodo , Cinética , Locus Cerúleo/efeitos dos fármacos , Masculino , Potenciais da Membrana/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Peptídeos/síntese química , Peptídeos/metabolismo , Ratos , Ratos Endogâmicos , Receptores de Galanina , Receptores dos Hormônios Gastrointestinais/efeitos dos fármacos , Medula Espinal/efeitos dos fármacosRESUMO
The galanin-receptor ligand M40 [galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide] binds with high affinity to [mono[125I]iodo-Tyr26]galanin-binding sites in hippocampal, hypothalamic, and spinal cord membranes and in membranes from Rin m5F rat insulinoma cells (IC50 = 3-15 nM). Receptor autoradiographic studies show that M40 (1 microM) displaces [mono[125I]iodo-Tyr26]galanin from binding sites in the hippocampus, hypothalamus, and spinal cord. In the brain, M40 acts as a potent galanin-receptor antagonist: M40, in doses comparable to that of galanin, antagonizes the stimulatory effects of galanin on feeding, and it blocks the galaninergic inhibition of the scopolamine-induced acetylcholine release in the ventral hippocampus in vivo. In contrast, M40 completely fails to antagonize both the galanin-mediated inhibition of the glucose-induced insulin release in isolated mouse pancreatic islets and the inhibitory effects of galanin on the forskolin-stimulated accumulation of 3',5'-cAMP in Rin m5F cells; instead M40 is a weak agonist at the galanin receptors in these two systems. M40 acts as a weak antagonist of galanin in the spinal flexor reflex model. These results suggest that at least two subtypes of the galanin receptor may exist. Hypothalamic and hippocampal galanin receptors represent a putative central galanin-receptor subtype (GL-1-receptor) that is blocked by M40. The pancreatic galanin receptor may represent another subtype (GL-2-receptor) that recognizes M40, but as a weak agonist. The galanin receptors in the spinal cord occupy an intermediate position between these two putative subtypes.