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Biomedical subjects

R P Ahlquist

Publications and source records attributed to R P Ahlquist.

15 recordsLinked to original sources
PubMed1977

Role of neuronal and extraneuronal uptake in responses of rabbit iris dilator muscle to levarterenol and phenylephrine.

The roles of neuronal and extraneuronal uptake mechanisms in the response of iris dilator muscles of rabbit to levarterenol (norepinephrine) and phenylephrine were investigated. Chemical denervation with 6-hydroxydopamine was used to eliminate neuronal uptake. Exposure to corticosterone prior to and during exposure to levarterenol or phenylephrine was used to assess the importance of extraneuronal uptake. Dose-response curves and ED50 values for levarterenol or phenylephrine in control and 6-hydroxydopamine-denervated tissues, both in the presence and absence of corticosterone, are shown. Curves illustrating the decay of tension on washout of levarterenol or phenylephrine from treated tissues were analyzed. 6-Hydroxydopamine denervation affected the response to levarterenol more than that to phenylephrine. Washout of both agonists was slower after 6-hydroxydopamine pretreatment, and washout of phenylephrine was more rapid when corticosterone was present. These data indicate that extraneuronal uptake in iris dilator muscles was more important in determining the response to phenylephrine than to levarterenol and that neuronal uptake was more important in determining tissue responsiveness to levarterenol than to phenylephrine.

Animals↗
PubMed1977

Present state of alpha and beta adrenergic drugs III. Beta blocking agents.

The beta blocking agents are valuable drugs in cardiology. They are effective in any fast arrhythmia. Together with nitroglycerin, beta blockers are drugs of first choice in angina. As antihypertensives, they have advantages that should make them drugs of first choice. For migraine the beta blockers are equal to any other type of drug. With more study their place in treating anxiety will be clarified. And without question other uses will be found. It is difficult for this author to understand the attitude of the FDA to this class of drugs. To limit the American physician to only one drug in this large group of drugs is unheard of. Although it can be argued that propranolol is the best one, there are obvious cases where another drug would be better. For example, propranolol induces nightmares in a few patients. There is evidence to show that timolol does this less frequently. FDA delay in approval of propranolol for essential hypertension is totally incomprehensible. Other approved drugs are less effective and much more toxic. Propranolol, and the other beta blockers, are safe and effective. The adverse beta effects are easily controlled or avoided. The other adverse effects are no more frequent than with any other class of drugs, and all are reversible. It is to be hoped that science and common sense will prevail over bureaucratic indecision.

Adrenergic beta-Antagonists↗
PubMed1977

Adrenoceptor sensitivity in disease as assessed through response to temperature alteration.

Drug receptors are usually defined in terms of specific agonists and blocking agents. The adrenoreceptor occurs in two forms, alpha and beta. From a pharmacologic point of view, this receptor concept has proved useful by allowing the development of new, selective agonists and blocking agents. From a physiologic viewpoint, there is no need for two receptors. Clinically, it is important to find out whether the pharmacologic adrenoceptors are immutable. Evidence is accumulating, both pro and con, regarding this point. Some of the effects of temperature on the response of the isolated dilator muscle of the rabbit iris to catecholamines are described. The following questions are asked: Is it not possible that there is only one adrenoceptor whose specific agonists are epinephrine or norepinephrine? Do the alpha and beta configuration depend only on the local environment? While no answers are given, it is concluded that these are clinically relavant questions.

Animals↗
PubMed1976

Present state of alpha and beta adrenergic drugs. II. The adrenergic blocking agents.

There are selective blocking agents (antagonists) for alpha receptors and beta receptors. These blocking agents prevent the response to injected agonists and neurogenically released norepinephrine. The principal cardiovascular response to alpha blockade is postural hypotension with reflexly induced cardiac stimulation. If neurogenic vasoconstriction is present, this will be removed. The principal cardiovascular response to beta blockade is bradycardia. If fast arrhythmias are present, these will be slowed. Beta blockade tends to increase peripheral resistance. Unless circulation is previously impaired this vasoconstrictive effect is insignificant.

Adrenergic alpha-Antagonists↗
PubMed1976

Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor.

The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians.

Adrenergic alpha-Agonists↗
PubMed1976

Role of neuronal and extraneuronal factors in temperature mediated responsiveness of adrenoceptors.

Changes in bath temperature caused changes in the adrenergic responsiveness of rabbit iris dilator muscle as indicated by shifts in dose-response curves along the log axis and changes in maximum responses. Responses of control tissues to an alpha agonist (norepinephrine) were increased at lower temperatures and responses to a beta agonist (isoprenaline) were increased at higher temperatures. Responses of control tissues were compared with responses of tissues pretreated with cocaine or with responses of adrenergically denervated tissues (chemical and surgical). Changes in ED50 values with temperature change are similar in control, cocaine pretreated or denervated muscles. In contrast, changes in maximum response with temperature change are reversed by cocaine pretreatment or denervation. Pretreatment of tissues with an inhibitor of catechol-o-methyl transferase (tropolone) or an inhibitor of monoamine oxidase (iproniazid) did not affect the temperature sensitivity of adrenoceptors. Also, responses to terbutaline, a beta agonist not susceptible to catechol-o-methyl transferase, changed with temperature. These data indicate that for rabbit iris dilator muscle both a neuronal and an extraneuronal component are involved in adrenoceptor response changes induced by temperature change and that changes in rates of activity of metabolizing enzymes are not involved.

Animals↗
PubMed1976

The influence of extracellular calcium on muscarinic receptors in vascular smooth muscle.

The present study was designed to investigate the influence of extracellular calcium (Ca++) on the affinity of cholinergic agonists and antagonists for muscarinic receptors in isolated rabbit aortic strips. Dose-response curves which demonstrate the effect of acetylcholine on the force of contraction in the presence of various Ca++ concentrations were made. The affinity constant was calculated and the intrinsic activity was determined at each of the different Ca++ concentrations used. In addition, the relationship between extracellular Ca++ and the pA2 value for atropine was determined. No apparent relationship between the affinity of acetylcholine for the cholinergic receptors and Ca++ concentration in vascular muscle was demonstrated. However, the intrinsic activity was altered when the extracellular Ca++ was varied. In addition, atropine was effective to the same degree both in the presence and complete absence of Ca++. These results are discussed in relation to the dependency of acetylcholine on extracellular Ca++ to induce contractile responses after receptor occupancy in vascular muscle.

Acetylcholine↗
PubMed1975

Adrenergic drug-receptor interaction in the presence of strontium (Sr++) in mammalian myocardium.

The specificity of Ca++ for the interaction of beta adrenergic agonists with their receptors in rabbit right atrial muscle was evaluated. This was accomplished by substituting Ca++ by an equimolar concentration of Sr++. Dose-response curves which demonstrate the effect of norepinephrine and isoproterenol on the rate of electrical activity in the presence of Ca++ or Sr++ were made. In addition, the antagonistic action of propranolol (1 X 10(-7) M) in a Ca++-containing or Sr++-containing medium was determined. The results clearly demonstrate that Sr++ can effectively substitute for Ca++ in maintaining electrical and mechanical activity in cardiac muscle. Also, norepinephrine and isoproterenol can increase the rate of electrical activity in a Ca++ or Sr++-containing medium. This effect of these beta agonists is mediated through the beta-receptors since propranolol effectively blocked their action. It appears that Ca++ per se is not required for beta agonist or antagonist-receptor interaction in cardiac muscle. The results are discussed in relation to the dependency on extracellular Ca++ for beta agonists to cause a change in the rate of electrical activity after receptor occupancy.

Adrenergic beta-Agonists↗
PubMed1975

Metabolic inhibition and adrenoceptor interconversion.

The adrenergic receptor responses of isolated strips of iris dilator muscle from rabbits were studied. An alpha agonist, norepinephrine and a beta agonist, isoprenaline, were used to assess adrenergic sensitivity before and after pretreatment of tissues with metabolic inhibitors at 22, 29 and 37 degrees C. The metabolic inhibitors used were iodoacetic acid and dinitrophenol. Temperature change altered adrenoceptor sensitivity in the same manner before and after metabolic inhibition. Iodoacetic acid (10.4 mug/ml) pretreatment increased both alpha and beta responses. Dinitrophenol (1.8 mug/ml) pretreatment increased alpha and decreased beta responsiveness. The results obtained indicate that some metabolic process altered by dinitrophenol may be involved in this adrenoceptor interconversion seen when temperature is changed. This supports the theory that local environment determines the drug sensitivity (alpha or beta) of a single adrenergic receptor.

Adrenergic alpha-Agonists↗