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PubMed2004

The phylogenetic position of Morotopithecus.

The phylogenetic relationship of the Ugandan Miocene hominoid Morotopithecus bishopi to fossil and living hominoids remains to be determined. In a cladistic approach to this question, we used three published Miocene character sets as the basis of a phylogenetic analysis: J. Hum. Evol. 29 (1995) 101; Function, Phylogeny, and Fossils: Miocene Hominoid Evolution and Adaptations, 1997, 389. Because these datasets often describe the same anatomy using different characters and states, three different datasets were created to reflect these alternatives. In addition, new postcranial characters describable in Morotopithecus were added to each of the above datasets and a fourth dataset was created using only postcranial characters. The most parsimonious tree(s) recovered in all analyses consistently placed Morotopithecus as a sister taxon to the extant great apes, with Hylobates sister to this clade. Morotopithecus was also consistently more derived than Proconsul, Afropithecus, and Kenyapithecus (as defined prior to the description of Equatorius), but less derived than Oreopithecus, Sivapithecus (only craniodentally) and Dryopithecus. These results imply that Morotopithecus is more derived than Hylobates. However, gibbons are believed to have branched off by at least 18 Ma while Morotopithecus is dated at >20.6 Ma. Possible explanations include: (1) the dating of the Morotopithecus material is too old; (2) the Hylobates divergence time has been underestimated; (3) the great ape condition, and not that of Hylobates, is primitive for hominoids; (4) the similarities of Morotopithecus and great apes are homoplasies. Given current evidence, the first possibility is unlikely, but it is not possible to choose definitively between the latter three possibilities. This conclusion is supported by the fact that despite the consistencies of the analyses, the addition of Morotopithecus and the use of different characters had a large effect on the placement of other Miocene taxa. This raises questions as to the robustness of the connections between Miocene taxa and extant hominoids since different results can be achieved by changing either a few characters, or by adding a single taxon. Many of the characters used to estimate phylogeny may need to be reassessed before a reliable assessment of the phylogenetic position of Morotopithecus can be achieved.

Animals↗
PubMed2004

An examination of dental development in Graecopithecus freybergi (=Ouranopithecus macedoniensis).

This study examined enamel thickness and dental development in Graecopithecus freybergi (=Ouranopithecus macedoniensis), a late Miocene hominoid from Greece. Comparative emphasis was placed on Proconsul, Afropithecus, Dryopithecus, Lufengpithecus, and Gigantopithecus, fossil apes that vary in enamel thickness and patterns of development. In addition, comparisons were made with Paranthropus to investigate reported similarities in enamel thickness. Several sections of a right lower third molar were generated, from which enamel thickness and aspects of the enamel and dentine microstructure were determined. Data from parallel sections shed light on the effects of section obliquity, which may influence determination of both enamel thickness and crown formation time. Graecopithecus has relatively thick enamel, greater than any fossil ape but less than Paranthropus, with which it does show similarity in prism path and Hunter-Schreger band morphology. Aspects of enamel microstructure, including the periodicity and daily secretion rate, are similar to most extant and fossil apes, especially Afropithecus. Total crown formation time was estimated to be 3.5 years, which is greater than published values for modern Homo, similar to Pan, and less than Gigantopithecus. Data on dentine secretion and extension rates suggest that coronal dentine formation was relatively slow, but comparative data are very limited. Graecopithecus shares a crown formation pattern with several thick-enamelled hominoids, in which cuspal enamel makes up a very large portion of crown area, is formed by a large cell cohort, and is formed in less than half of the total time of formation. In Paranthropus, this pattern appears to be even more extreme, which may result in thicker enamel formed in an even shorter time. Developmental similarities between Paranthropus and Graecopithecus are interpreted to be parallelisms due to similarities in the mechanical demands of their diets.

Animals↗
PubMed2004

Inferring hominoid and early hominid phylogeny using craniodental characters: the role of fossil taxa.

Recent discoveries of new fossil hominid species have been accompanied by several phylogenetic hypotheses. All of these hypotheses are based on a consideration of hominid craniodental morphology. However, Collard and Wood (2000) suggested that cladograms derived from craniodental data are inconsistent with the prevailing hypothesis of ape phylogeny based on molecular data. The implication of their study is that craniodental characters are unreliable indicators of phylogeny in hominoids and fossil hominids but, notably, their analysis did not include extinct species. We report here on a cladistic analysis designed to test whether the inclusion of fossil taxa affects the ability of morphological characters to recover the molecular ape phylogeny. In the process of doing so, the study tests both Collard and Wood's (2000) hypothesis of character reliability, and the several recently proposed hypotheses of early hominid phylogeny. One hundred and ninety-eight craniodental characters were examined, including 109 traits that traditionally have been of interest in prior studies of hominoid and early hominid phylogeny, and 89 craniometric traits that represent size-corrected linear dimensions measured between standard cranial landmarks. The characters were partitioned into two data sets. One set contained all of the characters, and the other omitted the craniometric characters. Six parsimony analyses were performed; each data set was analyzed three times, once using an ingroup that consisted only of extant hominoids, a second time using an ingroup of extant hominoids and extinct early hominids, and a third time excluding Kenyanthropus platyops. Results suggest that the inclusion of fossil taxa can play a significant role in phylogenetic analysis. Analyses that examined only extant taxa produced most parsimonious cladograms that were inconsistent with the ape molecular tree. In contrast, analyses that included fossil hominids were consistent with that tree. This consistency refutes the basis for the hypothesis that craniodental characters are unreliable for reconstructing phylogenetic relationships. Regarding early hominids, the relationships of Sahelanthropus tchadensis and Ardipithecus ramidus were relatively unstable. However, there is tentative support for the hypotheses that S. tchadensis is the sister taxon of all other hominids. There is support for the hypothesis that A. anamensis is the sister taxon of all hominids except S. tchadensis and Ar. ramidus. There is no compelling support for the hypothesis that Kenyanthropus platyops shares especially close affinities with Homo rudolfensis. Rather, K. platyops is nested within the Homo + Paranthropus + Australopithecus africanus clade. If K. platyops is a valid species, these relationships suggest that Homo and Paranthropus are likely to have diverged from other hominids much earlier than previously supposed. There is no support for the hypothesis that A. garhi is either the sister taxon or direct ancestor of the genus Homo. Phylogenetic relationships indicate that Australopithecus is paraphyletic. Thus, A. anamensis and A. garhi should be allocated to new genera.

Animals↗
PubMed2005

Ontogenetic integration of the hominoid face.

By investigating similarity in cranial covariation patterns, it is possible to locate underlying functional and developmental causes for the patterning, and to make inferences about the evolutionary forces that have acted to produce the patterns. Furthermore, establishing where these covariation patterns may diverge in ontogeny can offer insight into when selection may have acted on development. Here, covariation patterns are compared among adult and non-adult members of the African ape/human clade, in order to address three questions. First, are integration patterns constant among adult African apes and humans? Second, are they are constant in non-adults--i.e. throughout ontogeny? Third, if they are not constant, when do they diverge? Measurements are obtained from 677 crania of adult and non-adult African apes and humans. In order to address the first two questions, correlation matrices and theoretical integration matrices are compared using matrix correlation methods. The third question is evaluated by comparing correlation and variance/covariance patterns, using matrix correlation and random skewers methods, respectively, between adjacent age categories within each species, and between equivalent age categories among the four species. Results show that the hominoids share a similar pattern of ontogenetic integration, suggesting that common developmental/functional integrative processes may play an important role in keeping covariance structure stable across this lineage. However, there are some important differences in the magnitude of integration and in phenotypic covariance structure among the species, which may provide some insight into how selection acted to differentiate humans from the great apes.

Adolescent↗
PubMed2006

Metric variation and sexual dimorphism in the dentition of Ouranopithecus macedoniensis.

The fossil sample attributed to the late Miocene hominoid taxon Ouranopithecus macedoniensis is characterized by a high degree of dental metric variation. As a result, some researchers support a multiple-species taxonomy for this sample. Other researchers do not think that the sample variation is too great to be accommodated within one species. This study examines variation and sexual dimorphism in mandibular canine and postcanine dental metrics of an Ouranopithecus sample. Bootstrapping (resampling with replacement) of extant hominoid dental metric data is performed to test the hypothesis that the coefficients of variation (CV) and the indices of sexual dimorphism (ISD) of the fossil sample are not significantly different from those of modern great apes. Variation and sexual dimorphism in Ouranopithecus M(1) dimensions were statistically different from those of all extant ape samples; however, most of the dental metrics of Ouranopithecus were neither more variable nor more sexually dimorphic than those of Gorilla and Pongo. Similarly high levels of mandibular molar variation are known to characterize other fossil hominoid species. The Ouranopithecus specimens are morphologically homogeneous and it is probable that all but one specimen included in this study are from a single population. It is unlikely that the sample includes specimens of two sympatric large-bodied hominoid species. For these reasons, a single-species hypothesis is not rejected for the Ouranopithecus macedoniensis material. Correlations between mandibular first molar tooth size dimorphism and body size dimorphism indicate that O. macedoniensis and other extinct hominoids were more sexually size dimorphic than any living great apes, which suggests that social behaviors and life history profiles of these species may have been different from those of living species.

Animals↗
PubMed2006

Hallucial convergence in early hominids.

There is a richly documented fossil record of the evolutionary transition from ape-sized brains that are less that one-third the size of modern humans through a series of intermediate-sized brains up to the modern range. The first report on the discovery of the foot of the Stw 573 skeleton emphasized the apparent transitional nature of its great toe [Clarke, R.J., Tobias, P.V., 1995. Sterkfontein Member 2 foot bones of the oldest South African hominid. Science 269, pp. 521-524]. The hallux appeared to be intermediate in its divergence between human-like adduction and ape-like abduction. A major part of this evidence is the medial encroachment of the metatarsal I facet on the medial cuneiform. This study quantifies the variability of this feature in extant hominoids and fossil hominids. The results are consistent with the view that all currently known hominids were specialized for bipedality and lacked the ape-like ability to oppose the great toe.

Animals↗
PubMed2006

Bone density spatial patterns in the distal radius reflect habitual hand postures adopted by quadrupedal primates.

Primates adopt diverse hand postures during terrestrial and above-branch quadrupedal locomotion--knuckle-walking, digitigrady, and palmigrady--that incorporate varying degrees of wrist dorsiflexion (i.e., extension). Although relationships between hand postures, wrist joint range of motion, and the external properties of wrist bones (e.g., surface morphology) have been examined, the relationship between hand postures and the internal properties of wrist bones (e.g., bone density) remains largely unexplored. Because articular joint surfaces transmit mechanical loads between conjoining limb bones, measures of density (e.g., magnitudes and patterns) in the subchondral cortical plate of bone of the distal radius can be used to evaluate load regimes experienced by the wrist joint in different hand postures. We assessed apparent (i.e. optical) density patterns in several extant catarrhine primate taxa partitioned into different hand posture groups: knuckle-walking apes, digitigrade monkeys, and palmigrade monkeys. Computed tomography osteoabsorptiometry (CT-OAM) was used to construct maximum intensity projection (MIP) maps of apparent densities. High apparent density areas were characterized relative to a dorsal-volar reference plane and compared across hand posture groups. All groups had large percentage areas of high apparent density in the dorsal region of the distal radial articular surface. Only knuckle-walking apes, however, had a large percentage area of high apparent density in the volar region of the distal radial articular surface. These patterns are consistent with radiocarpal articulations in specific hand postures as evidenced by available radiographic data and suggest that the different habitual hand postures adopted by monkeys and African apes during quadrupedal locomotion have different stereotypic loading patterns. This has implications for understanding the functional morphology and evolution of knuckle-walking and digitigrade hand postures in primates.

Animals↗
PubMed2006

The dart-throwing motion of the wrist: is it unique to humans?

Kinematic analysis has shown a near-stationary proximal carpal row during the dart-thrower's motion, which is believed to provide a stable platform for the generation of force and accuracy during certain power and precision grip activities. This finding is consistent with evidence in the human hand of adaptations that enabled effective manipulation of stones, cylindric wood, and bone tools for throwing and clubbing. There are at least two possible explanations for the observed human proximal carpal row kinematics. One is that it is retained from a previous common ancestor with great apes and previously adapted to some form of foraging or locomotor behavior involving the hands, but was recruited for tool use after we diverged from the apes. The second is that it evolved after our divergence from apes, in synchrony with adaptations in the human hand to the manipulation of tools, and central to the development of the human's unique ability to aim and accelerate tools and weapons.

Adaptation, Physiological↗
PubMed2005

Crystal structures of the main peptidase from the SARS coronavirus inhibited by a substrate-like aza-peptide epoxide.

The main peptidase (M(pro)) from the coronavirus (CoV) causing severe acute respiratory syndrome (SARS) is one of the most attractive molecular targets for the development of anti-SARS agents. We report the irreversible inhibition of SARS-CoV M(pro) by an aza-peptide epoxide (APE; k(inact)/K(i) = 1900(+/-400) M(-1) s(-1)). The crystal structures of the M(pro):APE complex in the space groups C2 and P2(1)2(1)2(1) revealed the formation of a covalent bond between the catalytic Cys145 S(gamma) atom of the peptidase and the epoxide C3 atom of the inhibitor, substantiating the mode of action of this class of cysteine-peptidase inhibitors. The aza-peptide component of APE binds in the substrate-binding regions of M(pro) in a substrate-like manner, with excellent structural and chemical complementarity. In addition, the crystal structure of unbound M(pro) in the space group C2 revealed that the "N-fingers" (N-terminal residues 1 to 7) of both protomers of M(pro) are well defined and the substrate-binding regions of both protomers are in the catalytically competent conformation at the crystallization pH of 6.5, contrary to the previously determined crystal structures of unbound M(pro) in the space group P2(1).

Binding Sites↗
PubMed2006

Crystal structures reveal an induced-fit binding of a substrate-like Aza-peptide epoxide to SARS coronavirus main peptidase.

The SARS coronavirus main peptidase (SARS-CoV M(pro)) plays an essential role in the life-cycle of the virus and is a primary target for the development of anti-SARS agents. Here, we report the crystal structure of M(pro) at a resolution of 1.82 Angstroms, in space group P2(1) at pH 6.0. In contrast to the previously reported structure of M(pro) in the same space group at the same pH, the active sites and the S1 specificity pockets of both protomers in the structure of M(pro) reported here are in the catalytically competent conformation, suggesting their conformational flexibility. We report two crystal structures of M(pro) having an additional Ala at the N terminus of each protomer (M(+A(-1))(pro)), both at a resolution of 2.00 Angstroms, in space group P4(3)2(1)2: one unbound and one bound by a substrate-like aza-peptide epoxide (APE). In the unbound form, the active sites and the S1 specificity pockets of both protomers of M(+A(-1))(pro) are observed in a collapsed (catalytically incompetent) conformation; whereas they are in an open (catalytically competent) conformation in the APE-bound form. The observed conformational flexibility of the active sites and the S1 specificity pockets suggests that these parts of M(pro) exist in dynamic equilibrium. The structural data further suggest that the binding of APE to M(pro) follows an induced-fit model. The substrate likely also binds in an induced-fit manner in a process that may help drive the catalytic cycle.

Binding Sites↗
PubMed2004

AP endonuclease-independent DNA base excision repair in human cells.

The paradigm for repair of oxidized base lesions in genomes via the base excision repair (BER) pathway is based on studies in Escherichia coli, in which AP endonuclease (APE) removes all 3' blocking groups (including 3' phosphate) generated by DNA glycosylase/AP lyases after base excision. The recently discovered mammalian DNA glycosylase/AP lyases, NEIL1 and NEIL2, unlike the previously characterized OGG1 and NTH1, generate DNA strand breaks with 3' phosphate termini. Here we show that in mammalian cells, removal of the 3' phosphate is dependent on polynucleotide kinase (PNK), and not APE. NEIL1 stably interacts with other BER proteins, DNA polymerase beta (pol beta) and DNA ligase IIIalpha. The complex of NEIL1, pol beta, and DNA ligase IIIalpha together with PNK suggests coordination of NEIL1-initiated repair. That NEIL1/PNK could also repair the products of other DNA glycosylases suggests a broad role for this APE-independent BER pathway in mammals.

Cells, Cultured↗
PubMed2003

Primate cognition: from 'what now?' to 'what if?'.

The 'social brain' hypothesis has had a major impact on the study of comparative cognition. However, despite a strong sense, gained from both experimental and observational work, that monkeys and apes differ from each other, we are still no closer to understanding exactly how they differ. We hypothesize that the dispersed social systems characteristic of ape societies explains why monkeys and apes should differ cognitively. The increased cognitive control and analogical reasoning ability needed to cope with life in dispersed societies also suggests a possible route for human cognitive evolution. This hypothesis is supported by behavioural and neurobiological data, but we need more of both if we are to fully understand how our primate cousins see the world.

Journal Article↗
PubMed1999

Neuronal soma-dendritic and prejunctional M1-M4 receptors in gastrointestinal and genitourinary smooth muscle.

A variety of neurons in gastrointestinal and genitourinary smooth muscle express muscarinic auto- as well as heteroreceptors. These receptors are found on the soma and dendrites of many cholinergic, sympathetic and NANC neurons and on axon terminals. A given neuron may contain both excitatory and inhibitory presynaptic muscarinic receptors. The subtypes involved are species- and tissue-dependent, and neuronal M1 to M4 receptors have been shown to be expressed in smooth muscle tissues. In this study, the ability of several selective muscarinic receptor antagonists to inhibit the effect of arecaidine propargyl ester (APE) on prejunctional muscarinic receptors on sympathetic nerve endings in the rabbit anococcygeus muscle (RAM) was investigated to characterise the receptor subtype involved. Electrical field stimulation (EFS) resulted in a release of noradrenaline (NA) eliciting monophasic contractions due to stimulation of postjunctional alpha1-adrenoceptors. The selective muscarinic agonist APE did not reduce contractions to exogenous NA, but caused a concentration-related and N-methylatropine-sensitive inhibition of neurogenic responses. All muscarinic antagonists investigated failed to affect the EFS-induced contractions, but shifted the concentration-response curve of APE to the right in a parallel and surmountable fashion. Schild analysis yielded regression lines of unit slope, indicating competitive antagonism. The following rank order of antagonist potencies (pA2 values) was found: tripitramine (9.10) > AQ-RA 741 (8.26) > or = himbacine (8.04) > or = (S)-dimethindene (7.69) > pirenzepine (6.46) > or = p-F-HHSiD (6.27). A comparison of the pA2 values determined in the present study with literature binding and functional affinities obtained at native or recombinant M1 to M5 receptors strongly suggests that NA release from sympathetic nerve endings in RAM is inhibited by activation of prejunctional muscarinic M2 receptors.

Adrenergic alpha-Antagonists↗
PubMed2000

Asymmetries in cerebral width in nonhuman primate brains as revealed by magnetic resonance imaging (MRI).

A comparative study of asymmetries in cerebral width was conducted in a sample of great apes, Old World and New World monkeys. The brains of all subjects were scanned using magnetic resonance imaging (MRI) and the first axial slice above the third ventricle was identified. Measures of cerebral width were taken at distances of 10% and 30% of the length from the occipital and frontal poles. Cerebral widths were measured from the midline to the lateral surface of the brain for each area. The great apes exhibited a right-frontal and left-occipital directional asymmetry in cerebral width. In contrast, no significant mean directional asymmetries were found in either the Old or New World monkeys. The results in the great apes are consistent with previous reports of petalia asymmetries and suggest that the use of MRI is a valid approach to the assessment of neuroanatomical asymmetries in primates.

Animals↗
PubMed2000

Biodegradation of a nonylphenol ethoxylate by the autochthonous microflora in lake water with observations on the influence of light.

Alkylphenol polyethoxylates (APE) are routinely used as additives in pesticide formulations. Biodegradation of APEs results in the accumulation of persistent short chain mono-, di- and tri-ethoxylates (AP1EO, AP2EO AP3EO) that are more toxic than the parent compounds and potentially oestrogenic. Accumulation of persistent APE metabolites in shallow or ephemeral waters may pose a hazard to aquatic fauna. This study has followed the degradation and formation of individual oligomers in freshwater in static die-away tests with and without illumination. Over 33 days in darkness there was a progressive and complete loss of long chain oligomers (NP8-17EO), transient increases and subsequent loss of short to medium chain oligomers (NP4-7EO), and large persistent increases (approximately 1000%) in short chain oligomers (NP1-3EO). In the presence of illumination, biodegradation was retarded and heterotrophic bacterial proliferation was inhibited. After 33 days there was complete loss of long chain oligomers (NP9-17EO), incomplete loss of medium chain oligomers (NP6-8EO) and increases in short chain oligomers (NP1-5EO).

Bacteria↗
PubMed2003

Age at first molar emergence in early Miocene Afropithecus turkanensis and life-history evolution in the Hominoidea.

Among primates, age at first molar emergence is correlated with a variety of life history traits. Age at first molar emergence can therefore be used to broadly infer the life histories of fossil primate species. One method of determining age at first molar emergence is to determine the age at death of fossil individuals that were in the process of erupting their first molars. This was done for an infant partial mandible of Afropithecus turkanensis (KNM-MO 26) from the approximately 17.5 Ma site of Moruorot in Kenya. A range of estimates of age at death was calculated for this individual using the permanent lateral incisor germ preserved in its crypt, by combining the number and periodicity of lateral enamel perikymata with estimates of the duration of cuspal enamel formation and the duration of the postnatal delay in the inception of crown mineralization. Perikymata periodicity was determined using daily cross striations between adjacent Retzius lines in thin sections of two A. turkanensis molars from the nearby site of Kalodirr. Based on the position of the KNM-MO 26 M(1)in relation to the mandibular alveolar margin, it had not yet undergone gingival emergence. The projected time to gingival emergence was estimated based on radiographic studies of M(1)eruption in extant baboons and chimpanzees. The estimates of age at M(1)emergence in KNM-MO 26 range from 28.2 to 43.5 months, using minimum and average values from extant great apes and humans for the estimated growth parameters. Even the absolute minimum value is well outside the ranges of extant large Old World monkeys for which there are data (12.5 to <25 months), but is within the range of chimpanzees (25.7 to 48.0 months). It is inferred, therefore, that A. turkanensis had a life history profile broadly like that of Pan. This is additional evidence to that provided by Sivapithecus parvada (Function, Phylogeny, and Fossils: Miocene Hominoid Evolution and Adaptations, 1997, 173) that the prolonged life histories characteristic of extant apes were achieved early in the evolutionary history of the group. However, it is unclear at present whether life-history prolongation in apes represents the primitive catarrhine pace of life history extended through phyletic increase in body mass, or whether it is derived with respect to a primitive, size-adjusted life history that was broadly intermediate between those of extant hominoids and cercopithecoids. Life history evolution in primates as a whole may have occurred largely through a series of grade-shifts, with the establishment of fundamental life-history profiles early in the histories of major higher taxa. These may have included shifts that were largely body mass dependent, as well as those that occurred in the absence of significant changes in body mass.

Adaptation, Physiological↗
PubMed1997

Nonhuman primate models to evaluate vaccine safety and immunogenicity.

When considering preclinical studies to evaluate the safety and immunogenicity of putative vaccine candidates, such as nucleic acid vaccines, species most closely related to humans should be considered. Phylogenetically, the great apes (chimpanzees, orangutans, gorillas, and gibbons) are most closely related to humans. However, the great apes, which diverged from humans over 5 million years ago, represent endangered or threatened species that limits their utility in preclinical studies. In addition, cost considerations for using great apes in biomedical studies represents another serious limitation. The Old World monkeys, (macaques, baboons, mandrills, and mangabeys), diverged from humans over 15 million years ago. A number of the Old World monkey species including rhesus, cynomolgus, and African green monkeys, have also been employed in biomedical research to evaluate vaccine safety and immunogenicity. New World monkeys (aotus, owl, cebus monkeys, and marmosets) are the most phylogenetically divergent from humans, yet they have also been utilized to develop nonhuman primate models for a number of human infectious diseases and tumors. The advantages and disadvantages in selecting a particular nonhuman primate species for studies to evaluate DNA vaccine safety and immunogenicity are briefly discussed. Comparative immunology, reproductive physiology, endogenous infectious agents, and cost considerations are briefly described.

Animals↗
PubMed2002

Effects of Ba-Wei-Die-Huang-Wan on the cholinergic function and protein expression of M2 muscarinic receptor of the urinary bladder in diabetic rats.

The study investigated the effect of a traditional Chinese herbal preparation 'Ba-Wei-Die-Huang-Wan' on the cholinergic function of the urinary bladder in diabetic rats, as well as its influence on the protein expression of muscarinic M(2) receptors. Wistar rats were divided into three groups: (1) control rats; (2) 2-week streptozotocin-induced diabetic rats; and (3) diabetic rats treated with Ba-Wei-Die-Huang-Wan 26 mg/kg thrice daily for 3 days. A dose-response study was performed for bladder muscle strip contractile response to a muscarinic agonist, arecaidine propargyl ester (APE). The amount of M(2) receptor protein in the bladder was measured by Western immunoblotting using monoclonal antibodies. The bladder contractile response to APE was significantly increased in the diabetic rats compared to the control. The M(2) receptor protein density was also significantly higher by 106% (P < 0.01, n = 8) in diabetes. Ba-Wei-Die-Huang-Wan treatment significantly lowered the plasma glucose level of the diabetic rats. The increases in contractile response to APE as well as the M(2) receptor protein density were partially reversed by the treatment. In conclusion, there was an over-expression of M(2) receptor resulting in hyper-contractility in the bladder of diabetic rats. Ba-Wei-Die-Huang-Wan significantly alleviated the alterations.

Animals↗