SEARCH · PubMed Health

Results for “pathological subtype”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 415 records · Page 23Linked to original sources

PubMed2001

Assessment of axillary lymph node involvement in small breast cancer: analysis of 893 cases.

Axillary nodal involvement (ANI) remains an essential prognostic factor for breast cancer patients, as it implies the necessity of systemic adjuvant treatment and locoregional irradiation. Axillary dissection (AD) contributes to improved local disease control and may increase survival. However, AD results in a 10%-25% incidence of long-term side effects, particularly lymphedema. Moreover, many small primary lesions with low risk of ANI are now discovered by screening, and it is not clear whether AD should be used routinely in all such patients. Sentinel lymph node biopsy (SLNB) is a selective procedure that allows selective staging of the axilla with few side effects. However, indications for SLNB are not precisely defined yet, so some patients may be understaged and the axillary relapse rate may increase. This study was conducted to help clinicians assess the risk of ANI and analyzed six clinical and histological parameters to optimally recognize patients who might benefit from SLNB, with a minimal risk of false-negative rate. We retrospectively analyzed the ANI risk among 893 women treated by conservative surgery and radiation for T0, T1, or T2 invasive tumours < 3 cm in size. All patients underwent AD with sampling of a minimum of seven lymph nodes. In each case, we assessed the clinical and pathological tumor size, histological subtype (including grading), tumor location, age at diagnosis, and breast size. The global ANI rate in the entire cohort was 25.3%. In multivariate analysis, three variables were significantly predictive of the ANI risk: tumor size (P < 0.0001), histological subtype (P = 0.0005), and breast size (P = 0.004). By combining these parameters, we were able to define three categories of women with low (< 20%), intermediate (21%-25%), and high (> 25%) ANI risk. We suggest that women with nonpalpable (T0), T1 grade 1/2, and T2 < 3 cm tumors of medullary, mucinous, tubular, or papillary histological subtype are the best candidates for SLNB. For other patients with a higher ANI risk tumor, AD may still remain the best procedure to obtain accurate staging and definitive local control.

Adult↗

PubMedDate not supplied

[Acute autoimmune polyradiculoneuropathies].

Landry Guillain Barr Sthrol Syndrome (LGBS) is an acute autoimmune monophasic and selflimiting polyradiculoneuropathy affecting patients aged 19 to 59 years (1.7/100,000/year) more than below 18 year of age (0.8/100,000/year). Diagnostic criteria require: I. Progressive motor weakness of more than one limb, and II) absent muscle stretch reflexes. Features that strongly support the diagnosis are: 1. Cease of progression of weakness by 4 weeks, relative symmetrical involvement of the limbs, presence of mild sensory symptoms or signs, involvement of cranial nerves VII (50%) more than IX, X, III, IV and VI, recovery within 2 to 3 weeks after progression stop, presence of autonomic dysfunction, and absent of fever at onset; 2. Cerebral spinal fluid elevation of protein after first week of symptoms and less than 10 mononuclear leukocytes/mm3 except HIV seropositive patients (<50 cells/mm3), and 3. Nerve conduction slowing (<60% of normal ) or block at some point during the illness (80%), and increased distal motor latency up to 3 times above normal and F wave latency. There are four well defined clinical, pathological, neurophysiological and serological subtypes. Acute inflamatory demyelinating polyradiculoneuropathy (90%) and Miller Fisher syndrome (5%) are primarily demyelinating. Acute motor axonal neuropathy and acute motor sensory axonal neuropathy are primarily axonal (5%). Treatment includes supportive care and immunotherapy with high doses of intravenous IgG and plasmapheresis.

Autoantibodies↗

PubMedDate not supplied

Synchronous and metachronous retroperitoneal sarcomas: two case reports.

BACKGROUND: Retroperitoneal sarcomas represent less than 1% of all diagnosed human neoplasias. They are generally malignant and can infiltrate retroperitoneal structures. The value of chemotherapy and radiotherapy are difficult to evaluate and the dominating factor in the outcome is the ability to resect the tumor. A few patients develop distant metastases. Recurrence of sarcoma at the operative site and on peritoneal surfaces is a prominent cause of morbidity and mortality. CASE REPORTS: Here we report two patients who underwent surgery for retroperitoneal sarcoma. In each of them at least two primary retroperitoneal tumors were diagnosed. The neoplasms were histologically different, thus they cannot be considered local recurrence but rather primary tumors. CONCLUSION: This is the first report underlying the synchronous or metachronous presence of different histological subtypes in this neoplastic pathology. In explanation of the occurrence of satellite tumors and multiple primary tumors, a virus-associated etiology or polyclonality of the tumor or pluripotentiality of tumor stem cells should be considered.

Aged↗

PubMed2005

[Triptans in migraine--here and now (15 years after they were implemented in therapy)].

Migraine is one of the most common primary/idiopathic headaches as well as one of the most frequent complaints in the society. For the last 15 years there has been a significant change in the acute treatment of migraine attacks. It was a result of an extensive research on serotonin receptors, primarily their 5-HT(1B) and 5-HT(1D) subtypes, and on the pathological mechanisms underlying migraine headache. New drugs acting selectively, triptans, are not only more effective than traditional medicaments, common pain-killers (NSAID) and ergotamine, but are also much safer than non-selective and high affinity pharmaceuticals and ergotamine, which binds for a long time the 5-HT receptors, predominantly in the coronary arteries. The review shows main differences between particular triptans and discusses the principles of therapy, including contraindications.

Humans↗

PubMedDate not supplied

The problems in assessment of new treatment regimens of osteosarcoma.

The locations of the tumors that have been treated must be known if one is to sensibly assess the validity of therapeutic modalities. How the presence of metastases was excluded must be given, because patients without known metastases constitute the usual group of greatest interest. An indication of the validity of any series relates to the number of patients studied. Survivorship data based on projected five-year results should be assessed cautiously. Accuracy of the pathologic diagnosis is mandatory. Subtypes of osteosarcoma with behavior known to be different from the ordinary must be excluded. Specific details as to how the series was selected for study are necessary. It is impossible to assess accurately any published series unless the information specified in the foregoing is provided.

Bone Neoplasms↗

PubMed1993

Cloned somatostatin receptors: identification of subtype-selective peptides and demonstration of high affinity binding of linear peptides.

The recent molecular cloning of the genes encoding three somatostatin (SRIF) receptor subtypes has allowed for the individual expression of these receptors in mammalian cells and characterization of their respective pharmacological profiles. In the present study, we have investigated the affinities of a battery of SRIF analogues to bind to SRIF receptor subtypes SSTR1 (cloned somatostatin complex), SSTR2, and SSTR3, as well as their abilities to inhibit the release of growth hormone from anterior pituitary cells in vitro. We labeled SSTR1 and SSTR3 receptors expressed in Chinese hamster ovary and COS-1 cells, respectively, with the metabolically stable SRIF analogue 125I-CGP 23996. SSTR2 receptors expressed in Chinese hamster ovary cells were labeled with the SSTR2-specific radioligand 125I-MK-678. Inhibition studies were performed using SRIF analogues of differing structures, including hexapeptide analogues similar to MK-678, octapeptide analogues similar to SMS 201-995, pentapeptide analogues similar to c[Ahep-Phe-D-Trp-Lys-Thr(Bzl)] (SA), and linear SRIF analogues. SSTR1 bound SRIF and SRIF-28 with high affinity and the peptide SA and its structural analogues with low affinity. The hexapeptides did not interact with SSTR1 at concentrations as high as 1 microM, and only a few of the octapeptides or linear peptides bound, with very low affinities. In contrast, 125I-MK-678 binding to SSTR2 was potently inhibited by the hexapeptides, octapeptides, and some of the linear compounds, whereas SA and its analogues did not bind to SSTR2. The potencies of the various SRIF agonists to inhibit growth hormone release in vitro was highly correlated with their potencies to inhibit radioligand binding to SSTR2, but not to SSTR1 or SSTR3. SSTR3 bound analogues of each class but with moderate to low affinities, with the exception of several linear peptides and one of the octapeptides. We report for the first time the binding affinities of linear analogues of SRIF, some of which display subnanomolar affinities and are highly selective for SRIF receptor subtypes. Most importantly, these studies identify several peptide analogues that are highly potent, specific, and selective for individual subtypes of SRIF receptors. Such information, coupled with the knowledge of the distribution of these receptor subtypes in normal and pathological tissues, will be critical for more specific experimental and therapeutic interventions.

Amino Acid Sequence↗

PubMed1996

Angiotensin II--receptor subtypes characterization and pathophysiological implications.

In the past decade there have been considerable advances in basic knowledge of the renin-angiotensin system (RAS). The most important new development has been the appreciation of a tissue based RAS that can be independently regulated from the renal and vascular RAS. Greater insight into the mechanism by which angiotension-II (AII) exerts its action has been achieved through the study of molecular biology and pharmacological characterization of multiple receptor subtypes. This review summarises the features and distribution of several binding subtypes that may mediate the diverse functions of AII. Of these AT1 subtype is the most well known receptor which preferentially binds AII and AIII. The AT1 receptor site appears to mediate the classic angiotensin responses concerned with the body water balance and the maintenance of blood pressure. Less is known about the AT2 sites which also bind AII and AIII and may play a role in vascular growth. Recently, an AT3 has been discovered in cultured neuroblastoma cells and an AT4 site which preferentially binds AIV. It has been implicated in memory aquisition and retrieval and in the regulation of blood flow. Another important aspect covered is the primary and secondary messengers involved during the signal transduction after the binding of AII with receptors. A stress has also been given on the regulation of density and affinity of AII receptors by various physiological parametres as they affect the responses of RAS. Autoregulation by RAS, salt intake, development and aging and some of the hormones are important variables which could affect the AII receptors. Interactions of AII with various neuroeffector transmission involved in the regulation of water-electrolyte balance and BP regulation play an important role in the maintenance of the homeostasis. AII has been suggested to increase the NAergic transmission by enhancing synthesis, release, inhibiting reuptake by the presynaptic nerve terminals as well as enhancing cell responsiveness to the transmitter. The finding of existence of AII receptors in vagal afferent nerve terminals suggests that its baroreflex inhibitory effect is mediated by inhibiting neurotransmitter release at NTS in the baroreflex arc. Moreover, AII acts on the central receptors to stimulate AVP and ACTH secretion, drinking and peripherally increase synthesis and secretion of aldosterone. Interactions of RAS with kallikrein-kinin system and prostaglandins strongly support the existence of a balance between renal depressor and pressor substances. AII is now considered a growth promotor in cardiovascular tissues and the resultant vascular hypertrophy could contribute in the maintenance of hypertension. AII also plays a role in the kidney, not only as a regulator of hemodynamics but also in the structural changes occurring in a variety of renal disorders. In addition to the more well studied functions of RAS in RVH the review also highlights the potential contribution by the RAS to other clinically relevant syndromes such as aortoarterities induced RVH, hyperaldosteronism, heavy metal induced cardiovascular effects, diabetes mellitus and thyroid dysfunction. Although the receptor subtypes involved in these pathological states have not been definitely identified, research efforts in this direction are ongoing.

Animals↗

PubMed1996

Loss of transforming growth factor-beta type II receptor gene expression in primary human esophageal cancer.

Cell lines derived from carcinomas of the upper aero-digestive tract are typically refractory to transforming growth factor beta-mediated cell cycle arrest. Recently, we reported that the type II transforming growth factor beta receptor (T beta R-II) gene can be inactivated on the basis of missense mutations in such cell lines. These findings prompted us to investigate the molecular status of the T beta R-II gene in primary tumor specimens. Among 21 of 24 evaluable primary esophageal carcinomas, there were 6 cases (28.5%; 95% confidence interval, 11% to 52%) in which T beta R-II transcripts were low or undetectable by a reverse transcription PCR assay. In one of these cases, we were able to ascribe the loss of T beta R-II gene expression to high-density methylation of promoter sequences. We failed to detect any mutations within the open reading frame of the remaining tumors that expressed T beta R-II mRNA. In this relatively small series of cases, loss of T beta R-II expression was independent of pathologic tumor stage, histologic subtype, or outcome of patients with esophageal cancer. Thus, loss of expression of the T beta R-II gene appears to be the predominant mechanism through which this gene is inactivated in esophageal cancer.

Base Sequence↗

PubMed2005

Somatostatin receptors in primary human breast cancer: quantitative analysis of mRNA for subtypes 1--5 and correlation with receptor protein expression and tumor pathology.

Somatostatin receptors (SSTRs) have been identified in most hormone-producing tumors as well as in breast cancer. In the present study, we determined SSTR1-5 expression in primary ductal NOS breast tumors through semi-quantitative RT-PCR and immunocytochemistry. The results from the analysis of 98 samples were correlated with several key histological markers and receptor expression. All five SSTR subtypes are variably expressed at the mRNA level in breast tumors with 91% of samples showing SSTR1, 98% SSTR2, 96% SSTR3, 76% SSTR4, and 54% SSTR5. SSTR1-5 are localized to both tumor cells and the surrounding peritumoral regions as detected by immunocytochemistry. Levels of SSTR mRNA, when corrected for beta-actin levels, were highest for SSTR3 followed by SSTR1, SSTR2, SSTR5, and SSTR4. Furthermore, there was good correlation between mRNA and protein expression with 84% for SSTR1, 79% for SSTR2, 89% for SSTR3, 68% for SSTR4, 68% for SSTR5, and 78% for all five receptors. SSTR1, 2 and 4 were correlated with ER levels whereas SSTR2 showed an additional correlation with PR levels. These correlations were independent of patient age and histological grade. Moreover, using immunocytochemistry, blood vessels exhibited receptor-specific localization for SSTR2 and SSTR5. Our results indicate significant correlations between mRNA and protein expression along with receptor-specific correlations with histological markers as well as ER and PR levels. Differential distribution of SSTR subtypes in tumors and receptor-specific expression in vascular structures may be considered as a novel diagnosis for breast tumors with receptor subtype agonists.

Adult↗

PubMed2006

Muscarinic receptors in the ocular surface.

PURPOSE OF REVIEW: A wide distribution of the eye's muscarinic receptor system has been found and several roles for the muscarinic system in the eye proposed, although functional consequences of muscarinic receptor activation are not always fully characterized. The present paper reviews current knowledge about the presence of muscarinic receptors in the ocular surface and the implication of alterations on their expression and/or functioning in eye diseases. RECENT FINDINGS: Several authors have described alterations in muscarinic receptor subtype expression in the eye under pathological conditions. In conjunctiva of vernal keratoconjunctivitis patients, the expression of muscarinic receptor subtypes is altered in both the epithelium and stroma. Under proinflammatory conditions, M2-muscarinic receptor expression is upregulated in conjunctival epithelial cells in vitro. M3-muscarinic receptor altered distribution has been found in the lacrimal gland of NOD mice. SUMMARY: The cholinergic muscarinic system plays diverse roles. Alteration in the expression and/or functioning of muscarinic receptors may be implicated in the etiopathogenesis of some ocular diseases. Their pharmacological regulation may therefore have therapeutic value. Knowledge of the specific receptor subtypes expressed in each tissue may help to avoid some undesired secondary side effects in some cases when muscarinic agonists or antagonists are used.

Animals↗

PubMed1974

The epidemiological importance of 'ay' and 'ad' subtypes of the HB-Ag.

The distribution of the subtypes ;ay' and ;ad' has been assessed in 159 hepatitis B antigen (HB-Ag) positive subjects with a variety of associated hepatic conditions. A specific subtype could not be correlated with any particular hepatic pathology when the whole group was considered. However, the distribution of these two subtypes did vary according to the geographical origin of the subject or infection, or the presumed route of infection, so that there was an apparent association of one subtype with a certain disease state. Subtyping performed on 10 HB-Ag-positive households showed the subtype to be the same within nine, emphasizing the epidemiological rather than the pathological importance of the ;ay' and ;ad' subtypes of the HB-Ag.

Carrier State↗

PubMed1995

Roles of metabotropic glutamate receptors in brain plasticity and pathology.

In summary, the mGluRs are a large family of receptor subtypes with diverse properties in terms of transduction coupling, pharmacology, and anatomical distribution. Many divergent studies have demonstrated that activation of these receptors can result in either neuroprotection or neuropathology. We hypothesized that the mGluRs of astrocytes may have a role in determining the response following administration of mGluR agonists in vivo, and we have defined a suitable in vitro model for the study of these receptors. The experimental plasticity demonstrated in the astrocyte culture model may represent a more general principle that conditions in the microenvironment may differentially alter mGluR subtype expression as part of development, functional specialization, or pathology. This astrocyte model of receptor regulation provides a system suitable for studying the effects of specific growth factors, neurotrophins, cytokines, and other substances released by neurons and glia that may act in both autocrine and paracrine fashions. Alteration in the ratios of receptors by such variables could then modify future signaling properties and neuroglial interactions, a form of conditioning of the astrocytic response that would alter the physiological output following glutamate release. One measure of the value of this model will be its usefulness in stimulating the generation of hypotheses that can be tested in vivo. For example, the morphology of the astrocytes when cultured in the defined medium has similarities to the morphology of astrocytes undergoing reactive gliosis in pathological states. It is also interesting to note that treatments that have been reported to increase excitatory amino acid-stimulated PI hydrolysis in ex vivo brain slices (lesions, ischemia, and kindling) are accompanied by reactive gliosis. Those findings combined with the present in vitro results lead us to speculate that mGluR5 expression may also be altered in vivo during reactive gliosis. If so, it will be important to examine the functional consequences of such a change with regard to the astrocytic response to injury and maintaining the balance between excitatory transmission and excitotoxicity.

Animals↗

PubMed2004

Dietary factors and risk of non-Hodgkin lymphoma by histologic subtype: a case-control analysis.

There is speculation that etiologic heterogeneity exists among tumors classified as non-Hodgkin lymphoma (NHL), although it is not known whether diet-related associations vary between tumor subgroups. We analyzed data on 1,642 NHL cases and 5,039 controls aged 20 to 74 years from a population-based case-control study conducted in eight Canadian provinces to explore associations between dietary factors and NHL by histologic subtype. Dietary information was collected using a 69-item food frequency questionnaire. Tumors were categorized into histologic subtypes using the contents of pathology reports from the original histopathologic review of diagnostic material. Odds ratios (OR) relating consumption of dietary factors (divided into three categories) to each NHL subtype (diffuse, follicular, small lymphocytic, high grade, peripheral T cell, and unspecified lymphomas) were calculated using polytomous logistic regression. We found an increased risk of NHL with high (versus low) intake of processed meat (OR, 1.49), cheese (OR, 1.38), eggs (OR, 1.49), and dessert foods (OR, 1.24). Positive associations with NHL were also found for high consumption of total fat (OR, 1.28), saturated fat (OR, 1.29), and monounsaturated fat (OR, 1.27). Associations for consumption of some vegetables and fats were found to differ between lymphoma subtypes. Given the large number of diet/subtype comparisons done, however, the possibility that this heterogeneity arose by chance cannot be ruled out. In conclusion, these findings generally do not support the existence of etiologic heterogeneity between histologic subtypes of NHL in their associations with components of dietary intake.

Adult↗

PubMed2006

Clinical and pathologic features of fibroadenoma of the mastopathic type.

PURPOSE: Fibroadenoma with mastopathic change (FAM) is a relatively uncommon subtype of fibroadenoma of the breast, with a high incidence of pathological misdiagnosis. This histological subtype remains poorly understood because of its rarity. Many questions remain unanswered about its clinicopathological importance, especially in the differential diagnosis of breast cancers. METHODS: Among 218 breast fibroadenomas surgically resected as excisional biopsies at our institute between 1990 and 2004, 19 were pathologically diagnosed as FAM. We reviewed these 19 patients. RESULTS: The ages of the patients ranged from 20 to 51 years (mean 36.8 years). The tumor sizes ranged from 0.8 to 7 cm (mean 2.1 cm). Six of the 19 patients underwent core needle biopsy, resulting in a diagnosis of fibroadenoma in four patients and atypical ductal hyperplasia in two patients. Ultrasonography showed findings suggestive of solid tubular carcinoma in seven patients, fibroadenoma in ten patients, and unspecific malignant tumors in two. They were not specified clinically. CONCLUSION: Recognition of this distinctive variant of fibroadenoma is important because it resembles intraductal carcinoma and is increasing in incidence. It is crucial to distinguish FAM from intraductal carcinoma in biopsy specimens. Thus, not only pathologists but also clinicians must be able to recognize this type of fibroadenoma, and cooperate closely to establish an accurate diagnosis.

Adult↗

PubMed1998

Radiologic diagnosis and pathology of the spondyloarthropathies.

Five different subtypes of spondyloarthropathy (SpA) are now recognized. Clinical and radiologic involvement of the sacroiliac joint is an outstanding feature of the SpA, especially ankylosing spondylitis (AS). In this partly debilitating form of SpA a unique type of inflammatory axial involvement is observed which is characterized by inflammation and new bone formation at different spinal sites. In longstanding disease sacroiliitis, spondylitis and spondylodiscitis are easily recognized by conventional radiography and even better by computed tomography--especially when bony changes have already taken place. The advantage of dynamic magnetic resonance imaging (MRI) is to visualize morphologic changes and inflammation at the same time. This facilitates detection of sacroiliitis and spondylitis/spondylodiscitis at early time points. Hopefully, this will lead to other forms of therapy to prevent ankylosis of the spine. The origin of the granulation tissue infiltrating cartilage and bone in AS might be the synovium, the subchondrium or the bone marrow itself. T cells and macrophages seem to play an important role in this inflammatory process in which TNF-alpha is present in severe cases. The mechanisms responsible for the increased bone formation observed in the course of AS are unknown.

Animals↗

PubMed1981

Dysgerminoma with syncytiotrophoblastic giant cells. A histologically and clinically distinctive subtype of dysgerminoma.

The clinical and pathological features of six dysgerminomas containing syncytiotrophoblastic giant cells were studied; these represented 3% of the dysgerminomas in the AFIP files. Syncytiotrophoblastic giant cells, the distinguishing histological feature, were present either in clusters or were distributed diffusely. Human chorionic gonadotropin was demonstrated immunocytochemically within the cytoplasm of the syncytiotrophoblastic giant cells in both of the two tumors tested for it. Serum or urine gonadotropin titers, measured in four patients, were elevated in three, and two of these were thought to have ectopic pregnancies. All of the dysgerminomas were Stage Ia, and the six patients were well 1-14 years after treatment.

Adnexa Uteri↗

PubMed2003

Dietary and dietary-depressive subtypes of bulimia nervosa show differential symptom presentation, social impairment, comorbidity, and course of illness.

Research suggests that women with bulimia nervosa can be classified into dietary and dietary-depressive subtypes and that the latter show greater eating pathology, social impairment, comorbidity, and treatment nonresponse. The authors sought to replicate this subtyping scheme with an independent sample and to generate further evidence for the validity of this distinction. Analysis revealed dietary and dietary-depressive subtypes and indicated that the latter reported more current eating pathology, social impairment, and treatment seeking as well as greater psychiatric comorbidity and bulimic symptom persistence over a 5-year follow-up. This subtyping scheme had stronger concurrent and predictive validity than the purging-nonpurging distinction. Results provide further evidence for the reliability and validity of this subtyping scheme and suggest it has important clinical implications.

Adult↗

PubMed2001

Alpha-adrenoceptor subtypes.

Different studies have led to our present knowledge of the membrane receptors responsible for mediating the responses to the endogenous catecholamines. These receptors were initially differentiated into alpha - and beta-adrenoceptors. Alpha-adrenoceptors mediate most excitatory functions, and were in turn differentiated in the 1970s into alpha(1)- and alpha(2)-adrenoceptors. The alpha(1)-adrenoceptor type usually mediates responses in the effector organ. The alpha(2)-adrenoceptor type is located presynaptically and regulates the release of the neurotransmitter but it is also present in postsynaptical locations. Both alpha-adrenoceptors are important for the control of vascular tone, but we now know that neither alpha(1)- nor alpha(2)-adrenoceptors constitute homogeneous groups. Each alpha-adrenoceptor type can be subdivided into different subtypes and in this review we have turned our attention to these. The alpha(1)- and the alpha(2)-adrenoceptor subtypes were previously defined pharmacologically by functional and binding studies, and later they were also isolated and identified using cloning methods. In fact, the study of alpha-adrenoceptors was revolutionized by the techniques of molecular biology which permitted us to establish the present classification. The present classification of alpha(1)-adrenoceptors stands as follows: alpha(1A)-adrenoceptor subtype (cloned alpha(1c) and redesignated alpha(1a/c)), alpha(1B)-adrenoceptor subtype (cloned alpha(1b)) and alpha(1D)-adrenoceptor subtype (cloned alpha(1d) and redesignated alpha(1a/d)). It has not been easy to establish the distribution of these alpha(1)-adrenoceptor subtypes in the various organs and tissues, or to define the functional response mediated by each one in the different species studied. Nevertheless it seems that the alpha(1A)-adrenoceptor subtype is more implicated in the maintenance of vascular basal tone and of arterial blood pressure in conscious animals, and the alpha(1B)-adrenoceptor subtype participates more in responses to exogenous agonists. It has also been observed that the expression of the alpha(1B)-adrenoceptor subtype can be modified in pathological situations and particular attention has been paid to the regulation of expression of this receptor. The present classification of alpha(2)-adrenoceptors stands as follows: alpha(2A/D)-adrenoceptor subtype (today it is accepted that the alpha(2A)-adrenoceptor subtype and the alpha(2D)-adrenoceptor subtype are the same receptor but they were identified in different species: the alpha(2A) in human and the alpha(2D) in rat); alpha(2B)-adrenoceptor subtype (cloned alpha(2b)) and alpha(2C)-adrenoceptor subtype (cloned alpha(2c)). Today we know that the alpha(2A/D)- and alpha(2B)-adrenoceptor subtypes in particular control arterial contraction, and that the alpha(2C)-adrenoceptor subtype is responsible above all for venous vasoconstriction. We also know that the alpha(2 A/D)-adrenoceptor subtype fundamentally mediates the central effects of the alpha(2)-adrenoceptor agonists. Despite the validity of the above-mentioned classification of the alpha(1)- and alpha(2)-adrenoceptors, it seems clear that the contractions of a large number of tissues including smooth muscle are mediated by more than one alpha-adrenoceptor subtype. Moreover, few ligands recognise only one alpha-adrenoceptor subtype and the lack of specifity in the different drugs for each one limits their administration in vivo and their therapeutic use.

Adrenergic alpha-Agonists↗