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Biomedical subjects

N Ali

Publications and source records attributed to N Ali.

At least 37 records · Page 2Linked to original sources
PubMed2000

Demonstration of functional requirement of polypyrimidine tract-binding protein by SELEX RNA during hepatitis C virus internal ribosome entry site-mediated translation initiation.

Polypyrimidine tract-binding protein (PTB) has been previously shown to physically interact with the hepatitis C virus (HCV) RNA genome at its 5'- and 3'-noncoding regions. Using high affinity SELEX RNA molecules, we present evidence for the functional requirement of PTB during HCV internal ribosome entry site (IRES)-controlled translation initiation. This study was carried out in rabbit reticulocyte translation lysates in which the HCV IRES-driven reporter RNA was introduced along with the PTB-specific SELEX RNA molecules. The SELEX RNAs specifically inhibited the HCV IRES function in the context of mono- and dicistronic mRNAs. The cap-dependent translation of a reporter (chloramphenicol acetyltransferase) RNA or naturally capped brome mosaic virus RNA, however, was not affected by the presence of SELEX during in vitro translation assays. The SELEX-mediated inhibition of the HCV IRES is shown to be relieved by the addition of recombinant human PTB in an add-back experiment. The in vivo requirement of PTB was further confirmed by cotransfection of Huh7 cells with reporter RNA and PTB-specific SELEX RNA. The HCV IRES activity was inhibited by the SELEX RNA in these cells, but not by an unrelated control RNA. Together, these results demonstrate the functional requirement of cellular PTB in HCV translation and further support the feasible use of SELEX RNA strategy in demonstrating the functional relevance of cellular protein(s) in complex biological processes.

Base Sequence↗
PubMed2000

Human La antigen is required for the hepatitis C virus internal ribosome entry site-mediated translation.

The 5'-noncoding region (5'-NCR) of the hepatitis C virus (HCV) RNA genome serves as an internal ribosome entry site (IRES) and mediates translation initiation in a cap-independent manner. Previously, we reported the interaction between La antigen and the HCV IRES, which appeared to occur in the context of initiator AUG. It was further shown that HCV IRES-mediated translation was stimulated in the presence of human La antigen. In this study, we have defined the cis- and trans-acting elements responsible for La-5'-NCR interactions and established the dependence of the HCV IRES efficiency on cellular La antigen. During the La-IRES interaction, initiator AUG but not the neighboring codons was found to be the direct target of La binding. The C terminus effector domain-dependent modulation of La binding to the HCV IRES is demonstrated by deletion and substitution mutagenesis of the protein. An RNA systematic evolution of ligands by exponential enrichment (SELEX), generated against La protein that selectively binds La in HeLa lysates and competes for the protein binding to the 5'-NCR, was used to demonstrate the requirement of La for the HCV IRES function in the context of mono- and dicistronic mRNAs. Sequestration of La antigen by the RNA SELEX in HeLa translation lysates blocked the HCV and poliovirus IRES-mediated translation in vitro. The functional requirement of La protein for the HCV IRES activity was further established in a liver-derived cell line and in an add-back experiment in which the inhibited IRES was rescued by recombinant human La. These results strongly argue for the novel role of La protein during selection of the initiator AUG and its participation during internal initiation of translation of the HCV RNA genome.

5' Untranslated Regions↗
PubMed2000

NMDA-induced changes in a cortical network in vivo are prevented by AMPA.

Analogues of glutamic acid including N-methyl-D-aspartic acid (NMDA) depolarise neurones of the cerebral cortex in vivo and thus change the size of the somatosensory evoked potentials (SEPs). The potentials recover rapidly despite maintained superfusion with NMDA, suggesting a form of neuronal desensitisation or network adaptation. In this study potentials were evoked at the cortical surface by electrical stimulation of the contralateral forepaw and compounds applied topically to the cortical surface by a cortical cup. NMDA at 50-250 microM caused a concentration-dependent decrease in the amplitude of the SEPs, with the highest concentration always abolishing them. AMPA at 50 microM did not affect evoked potentials when applied alone, but prevented the NMDA. Such AMPA-NMDA interactions were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and enhanced by cyclothiazide (which prevents AMPA desensitisation). Superfusion with potassium did not change sensitivity to NMDA. These results suggest that, in the rat cerebral cortex in vivo, activation of AMPA receptors can induce a loss of the network response to activation of NMDA receptors. Such a phenomenon may have physiological and therapeutic implications.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2000

Chest pain with nondiagnostic electrocardiogram in the emergency department: a randomized controlled trial of two cardiac marker regimens.

BACKGROUND: Early detection of acute myocardial infarction (AMI) may save lives. In the emergency setting, it is unclear whether the early use of certain cardiac markers (myoglobin and cardiac troponin I [cTnI]) assists in making appropriate decisions whether to admit or discharge patients with chest pain of possible ischemic cause who have nondiagnostic electrocardiograms (ECGs). We performed a study to determine whether the addition of new cardiac markers in the emergency department results in improved clinical decisions. METHODS: A single-blind randomized controlled trial was conducted between June 1997 and June 1998 in a tertiary care emergency department in Kingston, Ont. Of 296 patients aged 30 years or more who presented to the emergency department with chest pain and nondiagnostic ECGs, 146 were randomly assigned to the intervention group (determination of baseline creatine kinase [CK] level, CK MB fraction and cTnI level, and myoglobin level at baseline and at 2 hours) and 150 to the control group (determination of baseline CK level and CK MB fraction). Outcome measures included the rate of admission to the inpatient cardiology service and length of stay in the emergency department. RESULTS: Of the 296 patients, 34 (11.5%) received a diagnosis of AMI in the emergency department, and 92 (31.1%) had chest pain of noncardiac cause. Patients in the intervention group were less likely than those in the control group to be admitted to the cardiology service (67 [45.9%] v. 81 [54.0%]). The absolute difference in the proportion (8.1% [95% confidence interval -3.3 to 19.5]), although potentially important clinically, was not statistically significant. The length of stay in the emergency department was essentially the same in the 2 study groups. At 30 days, the proportions of patients with a diagnosis of recurrent angina (58.2% in the intervention group and 58.0% in the control group) and AMI (12.3% and 14.7%) were also similar. INTERPRETATION: The optimal cardiac marker panel to be used in the emergency department remains unknown. The addition of serial testing of myoglobin with cTnI confirmation to the standard panel did not substantially change the clinical management or outcomes of patients presenting with chest pain and nondiagnostic ECGs.

Adult↗
PubMed2000

Activation of particulate guanylate cyclase by adrenomedullin in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells.

We investigated the effects of adrenomedullin (ADM) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ADM increased cGMP accumulation in a time- and concentration- dependent manner. The peptide increased cGMP formation in the transformed cells by 405-fold as compared to 1. 6-fold in primary cultured CISM cells. The basal cGMP concentrations in both cell types were comparable. In addition, ADM increased cAMP accumulation in SV-CISM-2 cells and in primary cultured cells by 18. 9- and 5.8-fold, respectively. The ADM receptor antagonist, ADM(26-52), but not the atrial natriuretic peptide (ANP) receptor antagonist, anantin, inhibited ADM-induced cGMP formation. The phorbol ester, phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylate cyclases in smooth muscle, blocked ADM-stimulated cGMP accumulation. In contrast, inhibitors of the soluble guanylate cyclases, such as LY83583 and ODQ, and inhibitors of the nitric oxide cascade had little effect on ADM-stimulated cGMP production. The stimulatory effect of ADM on cGMP formation is due to activation of the guanylate cyclase system and not to a much reduced phosphodiesterase activity. ADM stimulated guanylate cyclase activity in membrane fractions isolated from SV-CISM-2 cells in a concentration-dependent manner with EC(50) value of 72 nM. Pertussis toxin, an activator of the G-protein, Gi, inhibited ADM-stimulated cGMP accumulation, whereas cholera toxin, a stimulator of the Gs G-protein and subsequently cAMP accumulation, had little effect. Pretreatment of the plasma membrane fraction with Gialpha antibody attenuated ADM-stimulated guanylate cyclase activity by 75%. We conclude that ADM increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ADM receptor and subsequent stimulation of a Gi-mediated membrane-bound guanylate cyclase.

Adjuvants, Immunologic↗
PubMed2000

Antileishmanial activities of stearylamine-bearing liposomes.

Here we report the activity of liposomes comprising egg phosphatidylcholine (PC) and stearylamine (SA) against Leishmania donovani parasites. Both promastigotes and intracellular amastigotes in vitro and in vivo were susceptible to SA-PC liposomes. A single dose of 55 mg of SA-PC liposomes/animal could significantly reduce the hepatic parasite burden by 85 and 68% against recent and established experimental visceral leishmaniasis, respectively, suggesting their strong therapeutic potential.

Amines↗
PubMed2000

Elective versus symptomatic antibiotic treatment in cystic fibrosis patients with chronic Pseudomonas infection of the lungs.

BACKGROUND: A previous retrospective study suggested that a policy of regular anti-pseudomonal antibiotic treatment improved pulmonary function and increased survival in patients with cystic fibrosis chronically infected with Pseudomonas species. The results of a prospective multicentre study to compare the effects on pulmonary function and mortality of three monthly elective anti-pseudomonal antibiotic treatment with conventional symptomatic treatment are reported. METHODS: Sixty patients with cystic fibrosis, chronically infected with P aeruginosa, were randomised to the two treatment arms (elective or symptomatic) and followed clinically at yearly reviews. The major end points were changes in forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC). Survival was a secondary end point. RESULTS: Patients in the symptomatic group received a mean of three antibiotic treatments each year and those in the elective group received four antibiotic treatments during each year of the study. No significant differences in FEV(1) and FVC were found between the two groups after three years. There was a statistically non-significant higher rate of deaths in the elective group (n = 4), three of which were associated with B cepacia infection, compared with the symptomatic group (n = 0). CONCLUSIONS: This study did not demonstrate an advantage of a policy of elective antibiotic treatment over symptomatic treatment in patients with cystic fibrosis chronically infected with Pseudomonas species.

Adolescent↗
PubMed2000

Transcultural nursing concepts and experiences in nursing curricula.

Future trends in the convergence of a multicultural world continue to intensify the need to educate nurses to deliver culturally focused care. A descriptive survey was conducted to examine curricular trends related to the teaching of transcultural nursing (TCN) in nursing curricula of baccalaureate and higher degree schools of nursing in the United States. Faculty development and qualifications to teach transcultural nursing were identified as well as methods for collaboration between schools of nursing. Although TCN concepts are incorporated into most curricula, wide variation exists as to content, depth, and level of integration. Implications call for collaboration with accrediting agencies, including state boards of nursing, to strengthen expected outcomes related to culture, curricular reviews of nursing courses regarding the incorporation of TCN concepts and experiences, collaboration on culturally focused field experiences, faculty development, and networking across schools to expand available resources.

Curriculum↗
PubMed2000

Induction of partial protection against Leishmania donovani by promastigote antigens in negatively charged liposomes.

Negatively charged liposomes, proposed as potential vaccine adjuvants, have been extensively studied in association with various antigens. In the present study, we investigated the adjuvanicity of negatively charged liposomes to enhance the protective immunity of membrane antigens of Leishmania donovani promastigotes (LAg). In comparison to the control mice immunized with phosphate-buffered saline and empty liposomes, immunization with free LAg led to significant levels of protection against infection with virulent promastigotes. Encapsulation of LAg in liposomes also induced effective protection. However, the level of protection by LAg-liposome was not significantly different from that induced by free LAg. Investigation of the immune responses showed, in contrast to free LAg, that immunization with LAg-liposome elicited strong antibody responses. IgG isotype analysis revealed the presence of all 4 isotypes. However, the titer of IgG1 was significantly higher than IgG2a, IgG2b, and IgG3. Following infection, stimulation of IgG and IgG isotypes did not differ in the different immunization groups. Delayed-type hypersensitivity (DTH) analysis after immunization showed significant induction by LAg and LAg-liposomes, in comparison to controls. With infection, again, the level of DTH in all the groups became almost comparable. Stimulation of insufficient cellular response, as reflected by DTH and potentiation of IgG1 over IgG2a, IgG2b, and IgG3 suggest a dominance of Th2 response with this liposome-antigen formulation, resulting in weak protection against visceral leishmaniasis.

Animals↗
PubMed1999

Opiate, cannabinoid, and eicosanoid signaling converges on common intracellular pathways nitric oxide coupling.

Scientific fields as they emerge initially appear to be unrelated to other projects even if they are in a similar area of interest. This is especially true in the case of opiate, cannabinoid, and eicosanoid signaling processes. In this limited speculative review, we attempt to examine aspects of their intracellular cascading signaling systems for their commonalities. We find intracellular calcium mobilization, nuclear factor kappa B involvement, adenylate cyclase activity, and, finally, constitutive nitric oxide release to be converging points for these signaling processes, occurring by separate and distinct receptor-mediated effector systems. Phosphokinase C, mitogen activated protein kinase, and cytosolic phospholipase A2 also represent points of common impact. In this regard, aspirin also appears to be involved in an aspect of this signaling convergence. We conclude that many of the physiological observations regarding the actions of these signaling molecules, for example, immunosuppression, neurotransmission, vasodilation, cellular adherence, and cytotoxicity, can now be understood by considering their converging biochemical cascades.

Animals↗
PubMed1999

Atrial natriuretic peptide provokes a dramatic increase in cyclic GMP formation and markedly inhibits muscarinic-stimulated Ca2+ mobilisation in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells.

We investigated the effects of cGMP-elevating agents, including atrial natriuretic peptide (ANP), C-type natriuretic peptide (CNP) and sodium nitroprusside (SNP), on cGMP accumulation and on carbachol (CCh)-stimulated intracellular calcium ([Ca2+]i) mobilisation in SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells and in primary cultured cat iris sphincter smooth muscle (CISM) cells. The stimulatory effects of the natriuretic peptides on cGMP production correlated well with their inhibitory effects on CCh-induced [Ca+1]i mobilisation, and these effects were significantly more pronounced in the SV-CISM-2 cells than in the CISM cells. Thus, ANP (1 microM) increased cGMP production in the SV-CISM-2 cells and CISM cells by 487- and 1.7-fold, respectively, and inhibited CCh-induced [Ca2+]i mobilisation by 95 and 3%, respectively. In the SV-CISM-2 cells, ANP and CNP dose dependently inhibited CCh-induced [Ca2+]i mobilisation with IC50 values of 156 and 412 nM, respectively, and dose dependently stimulated cGMP formation with EC50 values of 24 and 88 nM, respectively, suggesting that the inhibitory actions of the peptides are mediated through cGMP. Both ANP and CNP stimulated cGMP accumulation in a time-dependent manner. The potency of the cGMP-elevating agents were in the following order: ANP>>CNP>>SNP; these agents had no effect on cAMP accumulation. The inhibitory effects of the natriuretic peptides were mimicked by 8-Br-cGMP, a selective activator of cGMP-dependent protein kinase. LY83583, a soluble guanylyl cyclase inhibitor, significantly inhibited SNP-induced cGMP formation but had no effect on those of ANP and CNP. The basal activities of the guanylyl cyclase and the dissociation constant (Kd) and total receptor density (Bmax) values of the natriuretic peptide receptor for [125I]ANP binding were not significantly different between the two cell types. The cGMP system, as with the cAMP system, has a major inhibitory influence on the muscarinic responses in the iris sphincter smooth muscle cells, and SV-CISM-2 cells can serve as an excellent model for investigating the cross talk between cGMP and the Ca2+ signalling system.

Aminoquinolines↗
PubMed1999

Evaluation and application of a simple and rapid method for the analysis of aflatoxins in commercial foods from Malaysia and the Philippines.

For application to the analysis of aflatoxins (AF) in commercial peanut and corn products, the ISOLUTE multimode column (IMC, solid phase multifunctional column) method was validated by comparing with the modified Florisil column (MFC) method. Twenty-two peanut and eight corn products from Malaysia and the Philippines were analysed for AFB1, AFB2, AFG1 and AFG2 firstly by the MFC method and then by the IMC method. For peanut products, 14 out of 22 samples were positive by the two methods in the range of 1-378 micrograms/kg of AF, and correlation coefficients (r) for AFB1 and AFB2 were 0.987 and 0.997, respectively. For corn and corn products, all the samples were positive in the range of 1-130 micrograms/kg, and r values were 0.992 and 0.805 for AFB1 and AFB2 respectively. Thus, the results were significantly (p < 0.01) in close agreement, particularly for lower range of 1-50 micrograms/kg of AF concentrations in all the samples. For the occurrence of AF, 11 (65%) of peanut products from Malaysia were contaminated with AF at a mean level of 50 micrograms/kg (maximum 180 micrograms/kg) and two (40% products from the Philippines were contaminated with as high as 375 micrograms/kg and 177 micrograms/kg of AF, respectively. All the corn products from the Philippines were contaminated with AF at a mean level of 44 micrograms/kg (maximum 130 micrograms/kg). Contamination of commercial foods with high levels of AF is a very important issue to both the countries since these foods are very popular among children.

Aflatoxins↗
PubMed1999

Immunoglobulin subclass distribution and diagnostic value of Leishmania donovani antigen-specific immunoglobulin G3 in Indian kala-azar patients.

Visceral leishmaniasis, or kala-azar, a fatal tropical disease, remains problematic, as early diagnosis is difficult and treatment often results in drug resistance and relapse. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA), using leishmanial membrane antigenic extracts (LAg) to detect specific antibody responses in 25 untreated Indian visceral leishmaniasis patients. To investigate the pathogenetic significance of isotype markers in kala-azar, relative levels of specific immunoglobulin G (IgG), IgM, IgA, IgE, and IgG subclasses were analyzed under clinically established diseased conditions. Since LAg showed higher sensitivity for specific IgG than lysate, the immunoglobulin isotype responses were evaluated, with LAg as antigen. Compared to 60 controls, which included patients with malaria, tuberculosis, leprosy, and typhoid and healthy subjects, visceral leishmaniasis patients showed significantly higher IgG (100% sensitivity, 85% specificity), IgM (48% sensitivity, 100% specificity), and IgE (44% sensitivity, 98.3% specificity) responses. Low levels of IgA in visceral leishmaniasis patients contrasted with a 13-fold-higher reactivity in sera from patients with leprosy. Among IgG subclasses, IgG1, -3, and -4 responses were significantly higher in visceral leishmaniasis patients than in the controls. IgG2 response, however, was significantly higher (twofold) in leprosy than even visceral leishmaniasis patients. The rank orders for sensitivity (IgG = IgG1 = IgG3 = IgG4 > IgG2 > IgM > IgE > IgA) and specificity (IgM = IgG3 > IgE > IgG4 > IgG2 > IgG > IgG1 > IgA) for LAg-specific antibody responses suggest the potentiality of IgG3 as a diagnostic marker for visceral leishmaniasis.

Animals↗
PubMed1999

Differential decline in Leishmania membrane antigen-specific immunoglobulin G (IgG), IgM, IgE, and IgG subclass antibodies in Indian kala-azar patients after chemotherapy.

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar.

Adolescent↗
PubMed1999

Induction of growth inhibition and apoptosis in pancreatic cancer cells by auristatin-PE and gemcitabine.

Pancreatic adenocarcinoma is the fifth leading cause of cancer related deaths in the United States. Treatment for this disease has largely been unsuccessful, which may partly be due to insufficient data regarding the molecular mechanisms of chemotherapeutic drugs currently being used as single agents or in combined modality regimens. In this study, we investigated the molecular mechanisms by which auristatin-PE, a newly developed experimental agent, and gemcitabine, a commercially available anti-cancer agent, exert their inhibitory effects on pancreatic cancer cell lines containing wild-type p53 (HPAC) and mutant p53 (PANC-1). Our results showed that auristatin-PE and gemcitabine inhibited cell growth and induced cell cycle arrest in G2/M and S phase, respectively. Auristatin-PE also induced apoptosis in both cell lines. Western blot analysis showed that auristatin-PE up-regulated the expression of wt-p53, p21WAF1 and Bax, and down-regulated Bcl-2 and cyclin B in HPAC cells, while only up-regulation of p21WAF1 and Bax was observed in PANC-1 cells. These results suggest that auristatin-PE may induce apoptosis and p21WAF1 expression through p53-dependent or independent pathways, and that up-regulation of p21WAF1 and Bax and down-regulation of Bcl-2 may be the molecular mechanism through which auristatin-PE inhibits cell growth and induces apoptosis. Furthermore, the up-regulation of p21WAF1 and down-regulation of cyclin B may contribute to the G2/M cell cycle arrest. Combination of auristatin-PE and gemcitabine showed significantly greater inhibition of cell growth and up-regulated expression of p21WAF1 and Bax. From these results, we conclude that the selection of therapeutic agents based on their molecular mechanism may improve therapeutic outcome, and that auristatin-PE may be more effective in the treatment of pancreatic cancer when given in combination with gemcitabine, rather than as a single agent.

Adenocarcinoma↗
PubMed1999

Effects of adrenomedullin on cyclic AMP formation and on relaxation in iris sphincter smooth muscle.

PURPOSE: To determine whether iris sphincter and other tissues of the iris-ciliary body secrete adrenomedullin (ADM), a novel hypotensive peptide that is classified into the calcitonin gene-related peptide (CGRP) family and to determine the binding sites for ADM and compare the effects of ADM and CGRP in the absence and presence of their receptor antagonists on cAMP formation and relaxation in the iris sphincter. METHODS: Sphincter muscle was incubated in Krebs-Ringer bicarbonate buffer in the absence and presence of ADM for 10 minutes. Accumulation of cAMP in the tissue extract was determined by radioimmunoassay (RIA). The binding of [125I]ADM to iris sphincter membranes was carried out by rapid filtration. Distribution of ADM in the ocular tissues was determined by RIA. Changes in muscle tension were recorded isometrically. RESULTS: Immunoreactive ADM was present in all tissues of the cat iris-ciliary body. In the isolated cat iris sphincter, ADM increased cAMP accumulation in a time- (t1/2 = 2.2 minutes) and concentration- (EC50 = 13 nM) dependent manner, and this effect was sixfold more efficacious than CGRP. ADM, CGRP, vasoactive intestinal peptide, prostaglandin E2, isoproterenol, and forskolin increased cAMP formation in cat sphincter by 12.5-, 2-, 2.2-, 1-, 2.6-, and 2.4-fold, respectively. The rank of the effects of ADM on cAMP formation in iris sphincter isolated from different animal species was in the following order: cat > dog > bovine > human > rabbit. In the cat iris sphincter, the CGRP antagonist, CGRP(8 to 37), was more effective than the ADM antagonist, ADM (26 to 52), in inhibiting both ADM- and CGRP-induced cAMP formation. ADM and CGRP inhibited carbachol-induced contraction in a concentration-dependent manner with IC50 values of 10 and 90 nM, respectively. Both ADM and CGRP displaced the binding of [125I]ADM to sphincter membranes effectively, with IC50 values of 0.81 and 1.15 nM, respectively. CONCLUSIONS: In iris sphincter isolated from cat and other mammalian species including human, ADM is a much more efficacious activator of adenylate cyclase and a much more effective relaxant than CGRP. Its biological effects may be due to direct involvement of ADM receptors, but also to activation of CGRP receptors. Activation of ADM receptors by the peptide leads to concentration-dependent increases in cAMP accumulation and subsequent inhibition (relaxation) of smooth muscle contraction. These findings suggest a role for ADM as a local modulator of smooth muscle tone. A possible function for this potent hypotensive peptide in the regulation of intraocular pressure remains to be investigated.

Adenylyl Cyclases↗