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I C Smith

Publications and source records attributed to I C Smith.

At least 19 recordsLinked to original sources
PubMed2001

Magnetic resonance spectroscopy of the malignant prostate gland after radiotherapy: a histopathologic study of diagnostic validity.

PURPOSE: Accurate spatial representation of tumor clearance after conformal radiotherapy is an endpoint of clinical importance. Magnetic resonance spectroscopy (MRS) can diagnose malignancy in the untreated prostate gland through measurements of cellular metabolites. In this study we sought to describe spectral metabolic changes in prostatic tissue after radiotherapy and validate a multivariate analytic strategy (based on MRS) that could identify viable tumor. METHODS AND MATERIALS: Transrectal ultrasound-guided prostate biopsies from 35 patients were obtained 18-36 months after external beam radiotherapy. One hundred sixteen tissue specimens were subjected to 1H MRS, submitted to histopathology, and analyzed for correlation with a multivariate strategy specifically developed for biomedical spectra. RESULTS: The sensitivity and specificity of MRS in identifying a malignant biopsy were 88.9% and 92% respectively, with an overall classification accuracy of 91.4%. The diagnostic spectral regions identified by our algorithm included those due to choline, creatine, glutamine, and lipid. Citrate, an important discriminating resonance in the untreated prostate gland, was invisible in all spectra, regardless of histology. CONCLUSIONS: Although the spectral features of prostate tissue markedly change after radiotherapy, MRS combined with multivariate methods of analysis can accurately identify histologically malignant biopsies. MRS shows promise as a modality that could integrate three-dimensional measures of tumor response.

Aged↗
PubMed2001

Detection of drug-induced apoptosis and necrosis in human cervical carcinoma cells using 1H NMR spectroscopy.

Apoptosis and necrosis need to be differentiated in order to distinguish drug-induced cell death from spontaneous cell death due to hypoxia. The ability to differentiate between these two modes of cell death, especially at an early stage in the process, could have a significant impact on accessing the outcome of anticancer drug therapy in the clinic. Nuclear magnetic resonance spectroscopy was used to distinguish apoptosis from necrosis in human cervical carcinoma (HeLa) cells. Apoptosis was induced by treatment with the topoisomerase II inhibitor etoposide, whereas necrosis was induced by the use of ethacrynic acid or cytochalasin B. We found that the intensity of the methylene resonance increases significantly as early as 6 h after the onset of apoptosis, but that no such changes occur during necrosis. The spectral intensity ratio of the methylene to methyl resonances also shows a high correlation with the percentage of apoptotic cells in the sample (r2=0.965, P<0.003).

Apoptosis↗
PubMed2001

The use of 1H magnetic resonance spectroscopy in inflammatory bowel diseases: distinguishing ulcerative colitis from Crohn's disease.

OBJECTIVES: The distinction between the two major forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn's disease is sometimes difficult and may lead to a diagnosis of indeterminate colitis. We have used 1H magnetic resonance spectroscopy (MRS) combined with multivariate methods of spectral data analysis to differentiate UC from Crohn's disease and to evaluate normal-appearing mucosa in IBD. METHODS: Colon mucosal biopsies (45 UC and 31 Crohn's disease) were submitted to 1H MRS, and multivariate analysis was applied to distinguish the two diseases. A second study was performed to test endoscopically and histologically normal biopsies from IBD patients. A classifier was developed by training on 101 spectra (76 inflamed IBD tissues and 25 normal control tissues). The spectra of 38 biopsies obtained from endoscopically and histologically normal areas of the colons of patients with IBD were put into the validation test set. RESULTS: The classification accuracy between UC and Crohn's disease was 98.6%, with only one case of Crohn's disease and no cases of UC misclassified. The diagnostic spectral regions identified by our algorithm included those for taurine, lysine, and lipid. In the second study, the classification accuracy between normal controls and IBD was 97.9%. Only 47.4% of the endoscopically and histologically normal IBD tissue spectra were classified as true normals; 34.2% showed "abnormal" magnetic resonance spectral profiles, and the remaining 18.4% could not be classified unambiguously. CONCLUSIONS: There is a strong potential for MRS to be used in the accurate diagnosis of indeterminate colitis; it may also be sensitive in detecting preclinical inflammatory changes in the colon.

Adult↗
PubMed2001

Issues involved in research into the neoadjuvant treatment of breast cancer.

Randomized studies have failed to find convincing evidence that neo-adjuvant chemotherapy results in improved overall survival. This may be related to limited efficacy of the regimens used. A sequence of an anthracycline-based primary chemotherapy followed by docetaxel has shown promising results which are briefly discussed. The assessment of the efficacy of neoadjuvant therapy should be based on the evaluation of pathological response and a simple, reproducible method of grading differential response would be of great value. Positive identification of tumor stroma is essential in defining pathological complete response (pCR). This paper presents a grading scheme based purely on microscopic assessment which classifies patients into five groups with significantly different disease-free and overall survival. A system dividing patients into only two groups, i.e. those with pCR or those with any evidence of invasive tumor, may lose information of prognostic value. Assessing the response of metastatic disease in the lymph nodes, as well as response of the primary tumor, may further refine our ability to identify those patients likely to gain most from neoadjuvant chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Positron emission tomography using [(18)F]-fluorodeoxy-D-glucose to predict the pathologic response of breast cancer to primary chemotherapy.

PURPOSE: To determine whether [(18)F]-fluorodeoxy-D-glucose ([(18)F]-FDG) positron emission tomography (PET) can predict the pathologic response of primary and metastatic breast cancer to chemotherapy. PATIENTS AND METHODS: Thirty patients with noninflammatory, large (> 3 cm), or locally advanced breast cancers received eight doses of primary chemotherapy. Dynamic PET imaging was performed immediately before the first, second, and fifth doses and after the last dose of treatment. Primary tumors and involved axillary lymph nodes were identified, and the [(18)F]-FDG uptake values were calculated (expressed as semiquantitative dose uptake ratio [DUR] and influx constant [K]). Pathologic response was determined after chemotherapy by evaluation of surgical resection specimens. RESULTS: Thirty-one primary breast lesions were identified. The mean pretreatment DUR values of the eight lesions that achieved a complete microscopic pathologic response were significantly (P =.037) higher than those from less responsive lesions. The mean reduction in DUR after the first pulse of chemotherapy was significantly greater in lesions that achieved a partial (P =.013), complete macroscopic (P =.003), or complete microscopic (P =.001) pathologic response. PET after a single pulse of chemotherapy was able to predict complete pathologic response with a sensitivity of 90% and a specificity of 74%. Eleven patients had pathologic evidence of lymph node metastases. Mean pretreatment DUR values in the metastatic lesions that responded did not differ significantly from those that failed to respond (P =.076). However, mean pretreatment K values were significantly higher in ultimately responsive cancers (P =.037). The mean change in DUR and K after the first pulse of chemotherapy was significantly greater in responding lesions (DUR, P =.038; K, P =.012). CONCLUSION: [(18)F]-FDG PET imaging of primary and metastatic breast cancer after a single pulse of chemotherapy may be of value in the prediction of pathologic treatment response.

Adult↗
PubMed2000

Current and potential chemotherapeutic agents used for induction chemotherapy in the treatment of breast cancer.

A substantial proportion of breast cancers are large (<3 cm) or locally advanced (T3, T4, TXN2) at the time of initial presentation. The therapeutic goals that must be achieved in patients with such cancers are to obtain adequate local disease control so that surgery can be performed and to abolish occult distant metastases therefore improving survival. Over the past three decades conventional adjuvant chemotherapy regimens have been employed pre-operatively (neo-adjuvant or primary chemotherapy) to achieve these goals. Studies have now shown that the survival of patients who receive neo-adjuvant chemotherapy is comparable to that of those who receive the same chemotherapy regimen following surgery. It is also apparent that although clinical tumour response rates to neo-adjuvant chemotherapy may be high there is considerable scope for improvement in the corresponding pathological tumour response. Furthermore, data from major studies that have comprehensively evaluated the use of pre-operative chemotherapy now indicates that the pathological response of breast cancers following treatment is of far greater prognostic importance than the clinical response. Recent interests has focoused, therefore, on the implementation of more prolonged or dose intensive chemotherapy regimens with the aims of improving pathological response to treatment and ultimately overall survival. Newer antineoplastic agents are also becoming available that may be used alone or in combination with conventional therapies in order that tumor response may be improved. This review describes current and potential therapeutic agents that may be used for the induction therapy of breast cancer.

Antibiotics, Antineoplastic↗
PubMed1999

Functional characterization of alpha1-adrenoceptor subtypes in longitudinal and circular muscle of human vas deferens.

The alpha1-adrenoceptor subtype(s) mediating contraction to noradrenaline in longitudinal and circular muscle of human epididymal vas deferens was studied using competitive antagonists. The effects of the alkylating agents, phenoxybenzamine and chloroethylclonidine were also investigated. Noradrenaline evoked concentration-dependent contractions of longitudinal and circular muscle with comparable potencies (pD2; 5.6 and 5.5 respectively). The contractions in longitudinal and circular muscle respectively were inhibited by prazosin (pA2, 8.6 and pKB, 9.2), 5-methylurapidil (pKB, 8.7 and 9.1) and less potently by spiperone (pA2, 7.1) or BMY 7378 (pKB, 6.3 and 6.6). Contractions of the circular but not longitudinal muscle was comparatively insensitive to pretreatment with phenoxybenzamine. In contrast pretreatment with chloroethylclonidine reduced the contractions in both muscle types and also enhanced phenoxybenzamine-sensitivity in longitudinal but not circular muscle. The results suggest that contractions evoked by noradrenaline in both muscle types of human vas deferens is mediated via activation of alpha1-adrenoceptors with pharmacological profile of the alpha1A-subtype. However the involvement of alpha1A-adrenoceptor variants, such as the hypothesised alpha1L-subtype may underlie the differential effects of phenoxybenzamine in longitudinal and circular muscle. Factors contributing to chloroethylclonidine-sensitivity are discussed.

Adrenergic alpha-Agonists↗
PubMed1999

MR spectroscopy using multi-ring surface coils.

A spatially uniform B(1)-field is preferred for MR imaging and spectroscopy. Unfortunately, volume coils are sometimes unavailable, or do not provide adequate RF power or SNR for some applications. In quantitative MRS, mean metabolite concentration cannot be evaluated when the coil response is nonuniform, unless an assumption is made concerning the metabolite spatial distribution. It is well known that standard single-loop surface coils, although offering high SNR characteristics, have poor B(1) homogeneity. New multi-ring surface coils are proposed which produce a locally uniform B(1) field, with sensitivity and power requirements comparable to those of standard surface coils. MR spectroscopy using two and three-ring versions of this "local volume coil" result in spatial localization essentially identical to that obtained with a volume coil but with much improved RF power and SNR characteristics. When compared to standard surface coils, the multi-ring coil offers much improved water suppression and localization, as well as reduced outer voxel contamination, with only a small loss in SNR and moderate increase in SAR. In summary, the multi-ring coil operates midway between the volume coil and the standard surface coil, retaining the most advantageous properties of both. Magn Reson Med 42:655-664, 1999. Published 1999 Wiley-Liss, Inc.

Humans↗
PubMed1999

Stimulated anti-echo selection in spatially localized NMR spectroscopy.

Spectral localization using the stimulated-echo acquisition mode (STEAM) is one of the most popular methods in volume-localized in vivo NMR spectroscopy. The localized volume signal is generated via stimulated echoes from spins excited by three 90 degrees RF pulses, and the conventional STEAM sequence detects the stimulated-echo signal. From an analysis of the STEAM pulse sequence using the coherence transfer pathway formalism, stimulated anti-echoes are also formed by the same pulse sequence, which constitute the other half of the localized signal in the STEAM experiment. A new scheme of pulsed field gradients for the selection of stimulated anti-echoes was proposed, and localized spectroscopy in the stimulated anti-echo selection mode was achieved on a phantom and from in vivo rat brain.

Animals↗
PubMed1999

Pharmacomechanical coupling in rat vas deferens: effects of agents that modulate intracellular release of calcium and protein kinase C activation.

The effects of agents that modulate intracellular release of calcium and protein kinase C (PKC) activation on noradrenaline (NA)-induced contractions of epididymal vas deferens in calcium-free/EGTA (1 mM) medium were investigated. NA (100 microM) or methoxamine (100 microM) evoked repeatable contractions. Clonidine (100-300 microM) was ineffective. The contractions to NA were reduced by procaine (1-10 mM) but not by thapsigargin (0.1-30 microM), ryanodine (1-30 microM) or TMB-8 (1-30 microM). Contractions to cumulative additions of NA (1-100 microM) were enhanced in the presence of cyclopiazonic acid (10 & 30 microM) but not ryanodine (10 & 30 microM). Sequential contractions to NA were not blocked by PKC inhibitors, calphostin C (1 microM) or Ro 31-8220 (1-30 microM) but were reduced by H-7 (1-30 microM), a broad spectrum protein kinase inhibitor. Although RT-PCR experiments detected mRNA for some Ca2+-dependent/DAG-activated and Ca2+-independent/DAG-activated PKC isoforms in epididymal vas deferens, the PKC activators, phorbol 12, 13-dibutyrate (100 microM) or phorbol 12-myristate 13-acetate (100 microM) failed to activate the tissues in calcium-free medium but enhanced subsequent contractions to NA. These results indicate a limited role for intracellular calcium stores and phorbol ester/DAG-sensitive PKC isoforms in NA-induced contraction of epididymal rat vas deferens in calcium-free medium. The results suggest that pharmacomechanical coupling triggered by NA may involve the sensitization of contractile myofilaments to Ca2+ or a Ca2+-independent mechanism. The possible involvement of Ca2+-independent/DAG-insensitive PKC isoforms and agonist-dependent but PKC-independent sensitization pathway is discussed.

Animals↗
PubMed1999

Characterization of alpha1-adrenoceptor subtypes mediating noradrenaline-induced contraction of rat epididymal vas deferens in calcium-free medium.

The alpha1-adrenoceptor subtype mediating noradrenaline (NA)-induced contractions of rat epididymal vas deferens in Ca2+-free/EGTA (1 mM) medium was studied using competitive antagonists. The effects of chloroethylclonidine (CEC) was investigated in Ca2+-free and normal Krebs' medium and RT-PCR was used to identify alpha1-adrenoceptor specific mRNA in epididymal vas deferens. In Ca2+-free medium, NA evoked sustained contractions but was less potent (pD2, 5.9) than in normal Krebs' medium (pD2, 7.3). The contractions in Ca2+-free medium were inhibited by prazosin (pA2, 9.3), 5-methylurapidil (pA2, 8.4), spiperone (pA2, 7.6) and BMY 7378 (pK(B), 6.8) consistent with activation of alpha1A-subtype. Repeated pretreatment with CEC (100 microM) reduced the potency of NA and maximum contractions in normal and Ca2+-free media. CEC-sensitivity in normal Krebs' medium was enhanced by prior treatment with phenoxybenzamine. mRNA for alpha1a- and alpha1d- but not alpha1b-adrenoceptors were detected in epididymal vas deferens. These results suggest that NA contracts the tissue in Ca2+-free medium by the stimulation of alpha1A-adrenoceptors. Two factors affecting CEC-sensitivity of NA-induced contractions in this tissue are discussed.

Adrenergic alpha-Agonists↗
PubMed1999

Different actions in the rat prostatic and epididymal vas deferens of cyclopiazonic acid or ryanodine on noradrenaline-induced contractions.

The effects of ryanodine, cyclopiazonic acid (CPA), and nifedipine on noradrenaline (NA)-induced contractions were investigated to characterize the role of the sarcoplasmic reticulum (SR) in the epididymal and prostatic parts of the rat vas deferens. In the epididymal part, NA (0.1, 1, and 100 microM) evoked marked rhythmic contractions superimposed on a tonic response. NA (100 microM) evoked biphasic tonic contractions consisting of a fast (initial) component and delayed secondary components. Nifedipine (1 microM) suppressed the rhythmic activity and the contractions to low NA concentrations and markedly reduced the components of the response to NA (100 microM). Contractions of the epididymal part to NA (0.1, 1, and 100 microM) were not blocked by ryanodine (1-30 microM) or CPA (1-30 microM). The secondary component in the response to NA (100 microM) was enhanced by CPA (> or =10 microM). Thus in the epididymal part, NA stimulates contraction predominantly by mobilizing extracellular calcium. However, a residual nifedipine-insensitive contraction to NA (100 microM) was observed and was not blocked by ryanodine (30 microM) or CPA (30 microM). In the prostatic part, NA evoked mainly tonic contractions. The response to NA (100 microM) consisted of three distinct components. Nifedipine (1 microM) reduced the contractions to low concentrations of NA (0.1 and 1 microM) and all three components of the response to NA (100 microM). Contractions of the prostatic part to low concentrations of NA (0.1 and 1 microM) were not blocked by CPA (30 microM) or ryanodine (30 microM). The components of the response to NA (100 microM) were affected differently by the drugs. Ryanodine (17-30 microM) or CPA (1-30 microM) suppressed the initial component and reduced the second component. The third component was largely unaffected by CPA but reduced by ryanodine. In the additional presence of nifedipine (1 microM), the residual components of NA (100 microM) response were markedly reduced and the contractions to low concentrations of the agonist virtually abolished. These results suggest that NA contracts the prostatic part by mobilizing both extra- and intracellular calcium. These results show that NA-induced contractions of the epididymal and prostatic parts of the rat vas deferens differ in sensitivity to ryanodine or CPA. The results suggest that, during stimulation of the epididymal part, the SR functions mainly to buffer calcium entering through nifedipine-sensitive voltage-gated calcium channels. In contrast, in the prostatic part, the SR serves mainly as a source of calcium and contributes more to contractions evoked by higher concentrations of the agonist.

Analysis of Variance↗
PubMed1998

Caffeine- and noradrenaline-induced contractions of human vas deferens: contrasting effects of procaine, ryanodine and W-7.

1. The effects of ryanodine, procaine, and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) on noradrenaline (NA)- and caffeine-induced contractions of human vas deferens were investigated. 2. In the presence of nifedipine (1 microM), NA ( 100 microM) evoked biphasic contractions. Caffeine (20 mM) evoked repeatable tonic contractions. 3. Ryanodine (30 microM) inhibited the initial but not the secondary component of NA contractions. Procaine (1 and 10 mM) inhibited both components. Contractions induced by caffeine were unaffected by ryanodine or procaine. 4. The calmodulin antagonist W-7 (100 microM) reduced, in a reversible manner, both components of NA-induced response. Caffeine-induced contractions were also reduced in most preparations (8 of 11). In all preparations, contractions induced by caffeine were markedly inhibited after the washout of W-7. Higher doses of W-7 (300 microM) induced an increase in basal tension. 5. These results indicate that NA contracts the longitudinal muscle of human vas deferens by a ryanodine-sensitive calcium-induced calcium release (CICR) mechanism and, in addition, a ryanodine-insensitive pathway: both are sensitive to procaine. In contrast, contraction induced by caffeine is mediated by a pathway that is atypically insensitive to either ryanodine or procaine. The sensitivity of NA- and caffeine-induced contraction to W-7 suggests a role for calcium and its interaction with calmodulin in the response to both agents. The paradoxical action of W-7 is discussed.

Anesthetics, Local↗
PubMed1998

Gamma emission imaging in the management of breast disorders.

Breast cancer is the commonest malignancy to affect women. The malignant process may present clinicians with problems in establishing the diagnosis expeditiously, accurately staging the disease and assessing tumour response to primary systemic chemotherapy. Considerable recent interest has focused on the application of imaging techniques that utilize tumour-specific gamma-ray-emitting radiopharmaceuticals to resolve these problems. The wide availability of gamma camera systems makes single photon-imaging techniques, using radiopharmaceuticals incorporating conventional isotopes, attractive options. However, results concerning the detection of the primary breast cancer and the staging of axillary lymph nodes suggest that these techniques would appear to offer no significant advantages, when compared with those obtained using standard diagnostic methods. Dual gamma-ray-emission imaging by positron emission tomography (PET) may offer an alternative solution. Studies performed show that PET can accurately detect primary breast cancers, stage locoregional lymph nodes and visualize distant tumour metastases. Furthermore, PET may be able to monitor early tumour response to chemotherapy agents. It would appear, therefore, that dual gamma emission might have an important role to play in the management of patients with breast cancer.

Bone Neoplasms↗
PubMed1998

Hypercalcaemia in patients with cancer: aetiology and treatment.

Hypercalcaemia is one of the most common disorders occurring in patients with cancer and may have disabling symptoms. The mechanisms underlying hypercalcaemia associated with malignant disease, the symptoms attributable to and the treatment of this disorder are discussed in this paper.

Humans↗
PubMed1998

Electromechanical coupling in human vas deferens: effects of agents that modulate intracellular release of calcium.

1. The effects of ryanodine, cyclopiazonic acid (CPA) and caffeine on electromechanical coupling in human vas deferens were investigated. 2. High [K+]o (120 mM) evoked nifedipine-sensitive contractions of longitudinal and circular muscle which consisted of initial and secondary components. 3. Exposures to ryanodine (< or =10 microM) or CPA (< or = 3 microM) induced a change of basal tension, and higher doses (30 microM) induced intermittent rhythmic contractions of both muscle types in the quiescent tissue. In the presence of the drugs, contraction to high [K+]o was preceded by marked rhythmic activity. 4. In circular muscle, ryanodine (1-30 microM) or CPA (1-30 microM) reduced both components of contractions to high [K+]o. In longitudinal muscle, the drugs enhanced the initial component and prolonged the secondary component. High doses (> or = 10 microM) produced variable effects on the initial component. 5. Caffeine (20 mM) reliably contracted longitudinal, but not circular muscle. Pre-exposures to caffeine enhanced both components in the post-caffeine contractions of circular muscle to high [K+]o. In longitudinal muscle, only the initial component (post-caffeine) was enhanced. 6. Contractions evoked in longitudinal muscle by caffeine were not blocked by ryanodine (30 microM) or CPA (30 microM). However, the enhancement of post-caffeine contractions to high [K+]o was inhibited. 7. These results show that ryanodine and CPA produced comparable effects on the excitability of longitudinal and circular muscle in the quiescent tissue, but electromechanical coupling was affected differently. The findings suggest that the muscle types utilize different mechanisms to regulate elevations in cytosolic Ca2+ during stimulation. 8. Electromechanical coupling in both muscle types involves Ca2+ influx via nifedipine-sensitive voltage-operated calcium channels and activation of ryanodine-sensitive calcium-induced calcium release from the sarcoplasmic reticulum (SR). In longitudinal muscle, the SR also buffers increases in cytosolic Ca2+ via a pharmacologically distinct Ca2+ compartment (caffeine releasable but ryanodine/CPA-insensitive). In circular muscle, the SR (ryanodine/CPA-sensitive) serves mainly in the regulation of excitability of the quiescent tissue.

Caffeine↗
PubMed1998

Ryanodine- and cyclopiazonic acid-sensitive components in human vas deferens contractions to noradrenaline.

1. The role of calcium stores in noradrenaline- (NA) and caffeine-induced contractions of human vas deferens were investigated using ryanodine and cyclopiazonic acid (CPA) in the presence of the calcium antagonist, nifedipine (1 microM) or in calcium-free/EGTA (1 mM) medium. 2. In either media, NA (100 microM) evoked biphasic contractions of longitudinal muscle and tonic circular muscle contractions. Caffeine (20 mM) evoked longitudinal but not circular muscle contractions. 3. Ryanodine (1-30 microM) or CPA (1-30 microM) inhibited contractions of circular muscle, and the initial but not secondary component of longitudinal muscle contraction to NA. 4. In the presence of nifedipine, pre-exposure to caffeine caused a potentiation of circular muscle, and the initial but not secondary longitudinal muscle contractions to NA. The presence of ryanodine or CPA during the caffeine pre-exposures effectively blocked the potentiation of the initial component and reduced the secondary component of the subsequent responses to NA in longitudinal muscle. 5. In calcium-free media, caffeine pre-exposures had little effect on subsequent NA-induced contractions in circular muscle, but reduced both components in longitudinal muscle. The presence of ryanodine or CPA during caffeine pre-exposures produced no further effects on either component of the subsequent NA-induced contraction in longitudinal muscle. 6 In the presence of nifedipine or in calcium-free media, repeated applications of caffeine evoked contractions in longitudinal muscle which were not blocked by either ryanodine or CPA. 7. These results suggest that circular muscle contraction by NA and the initial component of longitudinal muscle to NA both utilize an intracellular pool of calcium that is triggered via a ryanodine-sensitive mechanism and replenished via a CPA-sensitive Ca2+-ATPase. 8. In longitudinal muscle, both the secondary component of its response to NA and contraction to caffeine appear to involve an unusual but pharmacologically distinct (ryanodine- and CPA-insensitive) pathway. 9. The quiescence to caffeine of circular muscle may be caused by a relative absence of the ryanodine- and CPA-insensitive pathway.

Adrenergic alpha-Agonists↗